Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
8.0
4.5
Journals
Cancers
Sections
Application of Bioinformatics in Cancers
share announcement

Application of Bioinformatics in Cancers

A topical collection in Cancers (ISSN 2072-6694). This collection belongs to the section "Cancer Informatics and Big Data".

Viewed by 239670

Editor

Dr. J. Chad Brenner

E-Mail Website
Collection Editor
Department of Otolaryngology—Head and Neck SurgeryDirector, Michigan Otolaryngology and Translational Oncology LaboratoryUniversity of Michigan Health Systems, Ann Arbor, MI 48109, USA
Interests: functional genomic; proteomic and bioinformatics approaches in cancer; sequencing the exomes and transcriptomes of head and neck cancer; drug sensitivities
Special Issues, Collections and Topics in MDPI journals

Topical Collection Information

Dear Colleagues,

Bioinformatic applications in cancer have rapidly evolved over the past several years. Ever since its initial implementation, next generation sequencing has altered our understanding of cancer biology, and the approaches to analyzing the more and more complex datasets have also become increasingly complex.  Routine bioinformatics pipelines now range from those that rapidly detect and predict the functional impact of molecular alterations, to those that quantify the changes in the tumor microenvironment. For example, several tools that analyze tumor–immune interactions have been successfully developed so as to assess the tumor infiltrating lymphocyte content, microsatellite instability, total mutational burden, and neoantigen presentation. The further complexity of the integrated omics-based analysis is also now coupled with the emergence of modern machine learning and network-based approaches for analyzing large datasets in the context of publicly available resources, such as the cancer genome atlas.

While much of the focus has so far been on annotating molecular alterations. as well as infiltrating cell types or cell states in ideal sequencing conditions, alternative and application-specific approaches are now emerging that improve on a wide variety of established analysis techniques. These include techniques that range from the improved quantification of the copy number and gene expression from formalin-fixed tissues. as well as applications that require a high sensitivity, such as the quantification of tumor mutations from liquid biopsies (circulating cell free DNA).  Further novel applications attempt to improve the ability to analyze the distribution and molecular impact of complicated genetic features, such as repetitive or transposable endogenous elements (e.g., LINE-1), as well as exogenous genetic elements (e.g., human papilloma virus).

As we develop a better understanding of the limitations of these new informatics approaches, we can ultimately hope to apply these techniques to the existing datasets, and build well-annotated databases of easily accessible information that can be leveraged in multi-variable analysis pipelines. Similar to the success of SIGdb and cBioPortal, this should help yield new diagnostic and prognostic/predictive biomarkers for standard interventional modalities, as well as emerging areas like immuno-oncology, and areas of unmet clinical need. This Topical Collection will highlight the current state-of-the-art in bioinformatics applications in cancer biology, and infer future prospects for improving informatics applications through artificial intelligence and machine learning approaches.

Dr. J. Chad Brenner
Collection Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the collection website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (59 papers)

Download All Papers

2024

Jump to: 2023, 2022, 2021, 2020, 2019

18 pages, 4885 KiB  
Article
Induction of Invasive Basal Phenotype in Triple-Negative Breast Cancers by Long Noncoding RNA BORG
by Farshad Niazi, Kimberly A. Parker, Sara J. Mason, Salendra Singh, William P. Schiemann and Saba Valadkhan
Cancers 2024, 16(18), 3241; https://doi.org/10.3390/cancers16183241 - 23 Sep 2024
Viewed by 818
Abstract
Background/Objectives: Long noncoding RNAs (lncRNAs) are known to play key roles in breast cancers; however, detailed mechanistic studies of lncRNA function have not been conducted in large cohorts of breast cancer tumors, nor has inter-donor and inter-subtype variability been taken into consideration for [...] Read more.
Background/Objectives: Long noncoding RNAs (lncRNAs) are known to play key roles in breast cancers; however, detailed mechanistic studies of lncRNA function have not been conducted in large cohorts of breast cancer tumors, nor has inter-donor and inter-subtype variability been taken into consideration for these analyses. Here we provide the first identification and annotation of the human BORG lncRNA gene. Methods/Results: Using multiple tumor cohorts of human breast cancers, we show that while BORG expression is strongly induced in breast tumors as compared to normal breast tissues, the extent of BORG induction varies widely between breast cancer subtypes and even between different tumors within the same subtype. Elevated levels of BORG in breast tumors are associated with the acquisition of core cancer aggression pathways, including those associated with basal tumor and pluripotency phenotypes and with epithelial–mesenchymal transition (EMT) programs. While a subset of BORG-associated pathways was present in high BORG-expressing tumors across all breast cancer subtypes, many were specific to tumors categorized as triple-negative breast cancers. Finally, we show that genes induced by heterologous expression of BORG in murine models of TNBC both in vitro and in vivo strongly overlap with those associated with high BORG expression levels in human TNBC tumors. Conclusion: Our findings implicate human BORG as a novel driver of the highly aggressive basal TNBC tumor phenotype. Full article
►▼ Show Figures

Figure 1

15 pages, 1494 KiB  
Article
Molecular Analysis of Salivary and Lacrimal Adenoid Cystic Carcinoma
by Sarah Powell, Karina Kulakova, Katie Hanratty, Rizwana Khan, Paula Casserly, John Crown, Naomi Walsh and Susan Kennedy
Cancers 2024, 16(16), 2868; https://doi.org/10.3390/cancers16162868 - 17 Aug 2024
Viewed by 898
Abstract
Adenoid cystic carcinoma (ACC) of head and neck origin is associated with slow but relentless progression and systemic metastasis, resulting in poor long-term survival rates. ACC does not respond to conventional chemotherapy. Determination of molecular drivers may provide a rational basis for personalized [...] Read more.
Adenoid cystic carcinoma (ACC) of head and neck origin is associated with slow but relentless progression and systemic metastasis, resulting in poor long-term survival rates. ACC does not respond to conventional chemotherapy. Determination of molecular drivers may provide a rational basis for personalized therapy. Herein, we investigate the clinical and detailed molecular genomic features of a cohort of patients treated in Ireland and correlate the site of origin, molecular features, and outcomes. Clinical and genomic landscapes of all patients diagnosed with ACC over a twenty-year period (2002–2022) in a single unit in Ireland were examined and analyzed using fluorescence in situ hybridization, DNA sequencing, and bioinformatic analysis. Fourteen patients were included for analysis. Eleven patients had primary salivary gland ACC and three primary lacrimal gland ACC; 76.9% of the analyzed tumors displayed evidence of NFIB-MYB rearrangement at the 6q23.3 locus; 35% had mutations in NOTCH pathway genes; 7% of patients had a NOTCH1 mutation, 14.3% NOTCH2 mutation, and 14.3% NOTCH3 mutation. The presence of epigenetic modifications in ACC patients significantly correlated with worse overall survival. Our study identifies genetic mutations and signaling pathways that drive ACC pathogenesis, representing potential molecular and therapeutic targets. Full article
►▼ Show Figures

Figure 1

14 pages, 856 KiB  
Article
A Probabilistic Approach to Estimate the Temporal Order of Pathway Mutations Accounting for Intra-Tumor Heterogeneity
by Menghan Wang, Yanqi Xie, Jinpeng Liu, Austin Li, Li Chen, Arnold Stromberg, Susanne M. Arnold, Chunming Liu and Chi Wang
Cancers 2024, 16(13), 2488; https://doi.org/10.3390/cancers16132488 - 8 Jul 2024
Viewed by 895
Abstract
The development of cancer involves the accumulation of somatic mutations in several essential biological pathways. Delineating the temporal order of pathway mutations during tumorigenesis is crucial for comprehending the biological mechanisms underlying cancer development and identifying potential targets for therapeutic intervention. Several computational [...] Read more.
The development of cancer involves the accumulation of somatic mutations in several essential biological pathways. Delineating the temporal order of pathway mutations during tumorigenesis is crucial for comprehending the biological mechanisms underlying cancer development and identifying potential targets for therapeutic intervention. Several computational and statistical methods have been introduced for estimating the order of somatic mutations based on mutation profile data from a cohort of patients. However, one major issue of current methods is that they do not take into account intra-tumor heterogeneity (ITH), which limits their ability to accurately discern the order of pathway mutations. To address this problem, we propose PATOPAI, a probabilistic approach to estimate the temporal order of mutations at the pathway level by incorporating ITH information as well as pathway and functional annotation information of mutations. PATOPAI uses a maximum likelihood approach to estimate the probability of pathway mutational events occurring in a specific sequence, wherein it focuses on the orders that are consistent with the phylogenetic structure of the tumors. Applications to whole exome sequencing data from The Cancer Genome Atlas (TCGA) illustrate our method’s ability to recover the temporal order of pathway mutations in several cancer types. Full article
►▼ Show Figures

Figure 1

13 pages, 3544 KiB  
Article
Identifying Candidate Gene Drivers Associated with Relapse in Pediatric T-Cell Acute Lymphoblastic Leukemia Using a Gene Co-Expression Network Approach
by Anthony Kypraios, Juba Bennour, Véronique Imbert, Léa David, Julien Calvo, Françoise Pflumio, Raphaël Bonnet, Marie Couralet, Virginie Magnone, Kevin Lebrigand, Pascal Barbry, Pierre S. Rohrlich and Jean-François Peyron
Cancers 2024, 16(9), 1667; https://doi.org/10.3390/cancers16091667 - 25 Apr 2024
Viewed by 1809
Abstract
Pediatric T-cell Acute Lymphoblastic Leukemia (T-ALL) relapses are still associated with a dismal outcome, justifying the search for new therapeutic targets and relapse biomarkers. Using single-cell RNA sequencing (scRNAseq) data from three paired samples of pediatric T-ALL at diagnosis and relapse, we first [...] Read more.
Pediatric T-cell Acute Lymphoblastic Leukemia (T-ALL) relapses are still associated with a dismal outcome, justifying the search for new therapeutic targets and relapse biomarkers. Using single-cell RNA sequencing (scRNAseq) data from three paired samples of pediatric T-ALL at diagnosis and relapse, we first conducted a high-dimensional weighted gene co-expression network analysis (hdWGCNA). This analysis highlighted several gene co-expression networks (GCNs) and identified relapse-associated hub genes, which are considered potential driver genes. Shared relapse-expressed genes were found to be related to antigen presentation (HLA, B2M), cytoskeleton remodeling (TUBB, TUBA1B), translation (ribosomal proteins, EIF1, EEF1B2), immune responses (MIF, EMP3), stress responses (UBC, HSP90AB1/AA1), metabolism (FTH1, NME1/2, ARCL4C), and transcriptional remodeling (NF-κB family genes, FOS-JUN, KLF2, or KLF6). We then utilized sparse partial least squares discriminant analysis to select from a pool of 481 unique leukemic hub genes, which are the genes most discriminant between diagnosis and relapse states (comprising 44, 35, and 31 genes, respectively, for each patient). Applying a Cox regression method to these patient-specific genes, along with transcriptomic and clinical data from the TARGET-ALL AALL0434 cohort, we generated three model gene signatures that efficiently identified relapsed patients within the cohort. Overall, our approach identified new potential relapse-associated genes and proposed three model gene signatures associated with lower survival rates for high-score patients. Full article
►▼ Show Figures

Figure 1

19 pages, 2585 KiB  
Article
Identification of Interpretable Clusters and Associated Signatures in Breast Cancer Single-Cell Data: A Topic Modeling Approach
by Gabriele Malagoli, Filippo Valle, Emmanuel Barillot, Michele Caselle and Loredana Martignetti
Cancers 2024, 16(7), 1350; https://doi.org/10.3390/cancers16071350 - 29 Mar 2024
Cited by 1 | Viewed by 1397
Abstract
Topic modeling is a popular technique in machine learning and natural language processing, where a corpus of text documents is classified into themes or topics using word frequency analysis. This approach has proven successful in various biological data analysis applications, such as predicting [...] Read more.
Topic modeling is a popular technique in machine learning and natural language processing, where a corpus of text documents is classified into themes or topics using word frequency analysis. This approach has proven successful in various biological data analysis applications, such as predicting cancer subtypes with high accuracy and identifying genes, enhancers, and stable cell types simultaneously from sparse single-cell epigenomics data. The advantage of using a topic model is that it not only serves as a clustering algorithm, but it can also explain clustering results by providing word probability distributions over topics. Our study proposes a novel topic modeling approach for clustering single cells and detecting topics (gene signatures) in single-cell datasets that measure multiple omics simultaneously. We applied this approach to examine the transcriptional heterogeneity of luminal and triple-negative breast cancer cells using patient-derived xenograft models with acquired resistance to chemotherapy and targeted therapy. Through this approach, we identified protein-coding genes and long non-coding RNAs (lncRNAs) that group thousands of cells into biologically similar clusters, accurately distinguishing drug-sensitive and -resistant breast cancer types. In comparison to standard state-of-the-art clustering analyses, our approach offers an optimal partitioning of genes into topics and cells into clusters simultaneously, producing easily interpretable clustering outcomes. Additionally, we demonstrate that an integrative clustering approach, which combines the information from mRNAs and lncRNAs treated as disjoint omics layers, enhances the accuracy of cell classification. Full article
►▼ Show Figures

Figure 1

16 pages, 1983 KiB  
Article
Tumour Size and Overall Survival in a Cohort of Patients with Unifocal Glioblastoma: A Uni- and Multivariable Prognostic Modelling and Resampling Study
by Kavi Fatania, Russell Frood, Hitesh Mistry, Susan C. Short, James O’Connor, Andrew F. Scarsbrook and Stuart Currie
Cancers 2024, 16(7), 1301; https://doi.org/10.3390/cancers16071301 - 27 Mar 2024
Viewed by 1001
Abstract
Published models inconsistently associate glioblastoma size with overall survival (OS). This study aimed to investigate the prognostic effect of tumour size in a large cohort of patients diagnosed with GBM and interrogate how sample size and non-linear transformations may impact on the likelihood [...] Read more.
Published models inconsistently associate glioblastoma size with overall survival (OS). This study aimed to investigate the prognostic effect of tumour size in a large cohort of patients diagnosed with GBM and interrogate how sample size and non-linear transformations may impact on the likelihood of finding a prognostic effect. In total, 279 patients with a IDH-wildtype unifocal WHO grade 4 GBM between 2014 and 2020 from a retrospective cohort were included. Uni-/multivariable association between core volume, whole volume (CV and WV), and diameter with OS was assessed with (1) Cox proportional hazard models +/− log transformation and (2) resampling with 1,000,000 repetitions and varying sample size to identify the percentage of models, which showed a significant effect of tumour size. Models adjusted for operation type and a diameter model adjusted for all clinical variables remained significant (p = 0.03). Multivariable resampling increased the significant effects (p < 0.05) of all size variables as sample size increased. Log transformation also had a large effect on the chances of a prognostic effect of WV. For models adjusted for operation type, 19.5% of WV vs. 26.3% log-WV (n = 50) and 69.9% WV and 89.9% log-WV (n = 279) were significant. In this large well-curated cohort, multivariable modelling and resampling suggest tumour volume is prognostic at larger sample sizes and with log transformation for WV. Full article
►▼ Show Figures

Figure 1

2023

Jump to: 2024, 2022, 2021, 2020, 2019

22 pages, 2187 KiB  
Article
Genomic Alterations, Gene Expression Profiles and Functional Enrichment of Normal-Karyotype Acute Myeloid Leukaemia Based on Targeted Next-Generation Sequencing
by Angeli Ambayya, Rozaimi Razali, Sarina Sulong, Ezzanie Suffya Zulkefli, Yee Yee Yap, Jameela Sathar and Rosline Hassan
Cancers 2023, 15(5), 1386; https://doi.org/10.3390/cancers15051386 - 22 Feb 2023
Viewed by 2329
Abstract
Characterising genomic variants is paramount in understanding the pathogenesis and heterogeneity of normal-karyotype acute myeloid leukaemia (AML-NK). In this study, clinically significant genomic biomarkers were ascertained using targeted DNA sequencing and RNA sequencing on eight AML-NK patients’ samples collected at disease presentation and [...] Read more.
Characterising genomic variants is paramount in understanding the pathogenesis and heterogeneity of normal-karyotype acute myeloid leukaemia (AML-NK). In this study, clinically significant genomic biomarkers were ascertained using targeted DNA sequencing and RNA sequencing on eight AML-NK patients’ samples collected at disease presentation and after complete remission. In silico and Sanger sequencing validations were performed to validate variants of interest, and they were followed by the performance of functional and pathway enrichment analyses for overrepresentation analysis of genes with somatic variants. Somatic variants involving 26 genes were identified and classified as follows: 18/42 (42.9%) as pathogenic, 4/42 (9.5%) as likely pathogenic, 4/42 (9.5%) as variants of unknown significance, 7/42 (16.7%) as likely benign and 9/42 (21.4%) as benign. Nine novel somatic variants were discovered, of which three were likely pathogenic, in the CEBPA gene with significant association with its upregulation. Transcription misregulation in cancer tops the affected pathways involving upstream genes (CEBPA and RUNX1) that were deregulated in most patients during disease presentation and were closely related to the most enriched molecular function gene ontology category, DNA-binding transcription activator activity RNA polymerase II-specific (GO:0001228). In summary, this study elucidated putative variants and their gene expression profiles along with functional and pathway enrichment in AML-NK patients. Full article
►▼ Show Figures

Figure 1

19 pages, 10478 KiB  
Article
Identification of a Novel Model for Predicting the Prognosis and Immune Response Based on Genes Related to Cuproptosis and Ferroptosis in Ovarian Cancer
by Ying Li, Tian Fang, Wanying Shan and Qinglei Gao
Cancers 2023, 15(3), 579; https://doi.org/10.3390/cancers15030579 - 18 Jan 2023
Cited by 6 | Viewed by 2335
Abstract
(1) Background: Ovarian cancer (OV) presents a high degree of malignancy and a poor prognosis. Cell death is necessary to maintain tissue function and morphology. Cuproptosis and ferroptosis are two novel forms of death, and we look forward to finding their relationship with [...] Read more.
(1) Background: Ovarian cancer (OV) presents a high degree of malignancy and a poor prognosis. Cell death is necessary to maintain tissue function and morphology. Cuproptosis and ferroptosis are two novel forms of death, and we look forward to finding their relationship with OV and providing guidance for treatment. (2) Methods: We derived information about OV from public databases. Based on cuproptosis-related and ferroptosis-related genes, a risk model was successfully constructed, and exceptional subtypes were identified. Next, various methods are applied to assess prognostic value and treatment sensitivity. Besides, the comprehensive analysis of the tumor environment, together with immune cell infiltration, immune function status, immune checkpoint, and human HLA genes, is expected to grant assistance for the prognosis and treatment of OV. (3) Results: Specific molecular subtypes and models possessed excellent potential to predict prognosis. Immune infiltration abundance varied between groups. The susceptibility of individuals to different chemotherapy drugs and immunotherapies could be predicted based on specific groups. (4) Conclusions: Our molecular subtypes and risk model, with strong immune prediction and prognostic prediction capabilities, are committed to guiding ovarian cancer treatment. Full article
►▼ Show Figures

Figure 1

25 pages, 8262 KiB  
Article
Revealing Prognostic and Immunotherapy-Sensitive Characteristics of a Novel Cuproptosis-Related LncRNA Model in Hepatocellular Carcinoma Patients by Genomic Analysis
by Zhenzhen Mao, Ye Nie, Weili Jia, Yanfang Wang, Jianhui Li, Tianchen Zhang, Xinjun Lei, Wen Shi, Wenjie Song and Xiao Zhang
Cancers 2023, 15(2), 544; https://doi.org/10.3390/cancers15020544 - 16 Jan 2023
Cited by 2 | Viewed by 2531
Abstract
Immunotherapy has shown strong anti-tumor activity in a subset of patients. However, many patients do not benefit from the treatment, and there is no effective method to identify sensitive immunotherapy patients. Cuproptosis as a non-apoptotic programmed cell death caused by excess copper, whether [...] Read more.
Immunotherapy has shown strong anti-tumor activity in a subset of patients. However, many patients do not benefit from the treatment, and there is no effective method to identify sensitive immunotherapy patients. Cuproptosis as a non-apoptotic programmed cell death caused by excess copper, whether it is related to tumor immunity has attracted our attention. In the study, we constructed the prognostic model of 9 cuproptosis-related LncRNAs (crLncRNAs) and assessed its predictive capability, preliminarily explored the potential mechanism causing treatment sensitivity difference between the high-/low-risk group. Our results revealed that the risk score was more effective than traditional clinical features in predicting the survival of HCC patients (AUC = 0.828). The low-risk group had more infiltration of immune cells (B cells, CD8+ T cells, CD4+ T cells), mainly with anti-tumor immune function (p < 0.05). It showed higher sensitivity to immune checkpoint inhibitors (ICIs) treatment (p < 0.001) which may exert the effect through the AL365361.1/hsa-miR-17-5p/NLRP3 axis. In addition, NLRP3 mutation-sensitive drugs (VNLG/124, sunitinib, linifanib) may have better clinical benefits in the high-risk group. All in all, the crLncRNAs model has excellent specificity and sensitivity, which can be used for classifying the therapy-sensitive population and predicting the prognosis of HCC patients. Full article
►▼ Show Figures

Figure 1

22 pages, 2948 KiB  
Article
Serum Mass Spectrometry Proteomics and Protein Set Identification in Response to FOLFOX-4 in Drug-Resistant Ovarian Carcinoma
by Domenico D’Arca, Leda Severi, Stefania Ferrari, Luca Dozza, Gaetano Marverti, Fulvio Magni, Clizia Chinello, Lisa Pagani, Lorenzo Tagliazucchi, Marco Villani, Gianluca d’Addese, Isabella Piga, Vincenza Conteduca, Lorena Rossi, Giorgia Gurioli, Ugo De Giorgi, Lorena Losi and Maria Paola Costi
Cancers 2023, 15(2), 412; https://doi.org/10.3390/cancers15020412 - 8 Jan 2023
Cited by 3 | Viewed by 3170
Abstract
Ovarian cancer is a highly lethal gynecological malignancy. Drug resistance rapidly occurs, and different therapeutic approaches are needed. So far, no biomarkers have been discovered to predict early response to therapies in the case of multi-treated ovarian cancer patients. The aim of our [...] Read more.
Ovarian cancer is a highly lethal gynecological malignancy. Drug resistance rapidly occurs, and different therapeutic approaches are needed. So far, no biomarkers have been discovered to predict early response to therapies in the case of multi-treated ovarian cancer patients. The aim of our investigation was to identify a protein panel and the molecular pathways involved in chemotherapy response through a combination of studying proteomics and network enrichment analysis by considering a subset of samples from a clinical setting. Differential mass spectrometry studies were performed on 14 serum samples from patients with heavily pretreated platinum-resistant ovarian cancer who received the FOLFOX-4 regimen as a salvage therapy. The serum was analyzed at baseline time (T0) before FOLFOX-4 treatment, and before the second cycle of treatment (T1), with the aim of understanding if it was possible, after a first treatment cycle, to detect significant proteome changes that could be associated with patients responses to therapy. A total of 291 shared expressed proteins was identified and 12 proteins were finally selected between patients who attained partial response or no-response to chemotherapy when both response to therapy and time dependence (T0, T1) were considered in the statistical analysis. The protein panel included APOL1, GSN, GFI1, LCATL, MNA, LYVE1, ROR1, SHBG, SOD3, TEC, VPS18, and ZNF573. Using a bioinformatics network enrichment approach and metanalysis study, relationships between serum and cellular proteins were identified. An analysis of protein networks was conducted and identified at least three biological processes with functional and therapeutic significance in ovarian cancer, including lipoproteins metabolic process, structural component modulation in relation to cellular apoptosis and autophagy, and cellular oxidative stress response. Five proteins were almost independent from the network (LYVE1, ROR1, TEC, GFI1, and ZNF573). All proteins were associated with response to drug-resistant ovarian cancer resistant and were mechanistically connected to the pathways associated with cancer arrest. These results can be the basis for extending a biomarker discovery process to a clinical trial, as an early predictive tool of chemo-response to FOLFOX-4 of heavily treated ovarian cancer patients and for supporting the oncologist to continue or to interrupt the therapy. Full article
►▼ Show Figures

Figure 1

2022

Jump to: 2024, 2023, 2021, 2020, 2019

23 pages, 5684 KiB  
Article
Comprehensive Analysis of DMRT3 as a Potential Biomarker Associated with the Immune Infiltration in a Pan-Cancer Analysis and Validation in Lung Adenocarcinoma
by Donghong Yang, Meilian Liu, Junhong Jiang, Yiping Luo, Yongcun Wang, Huoguang Chen, Dongbing Li, Dongliang Wang, Zhixiong Yang and Hualin Chen
Cancers 2022, 14(24), 6220; https://doi.org/10.3390/cancers14246220 - 16 Dec 2022
Cited by 14 | Viewed by 1996
Abstract
Doublesex and Mab-3 related Transcription Factor 3 (DMRT3) is associated with the prognosis of some tumors. It is possible to explore the role of DMRT3 in the cancer process using bioinformatic approaches and experimental validation. We comprehensively explored the clinical and immunological characteristics [...] Read more.
Doublesex and Mab-3 related Transcription Factor 3 (DMRT3) is associated with the prognosis of some tumors. It is possible to explore the role of DMRT3 in the cancer process using bioinformatic approaches and experimental validation. We comprehensively explored the clinical and immunological characteristics of DMRT3. The DMRT3 expression is abnormal in human cancers and correlates with clinical staging. A high DMRT3 expression is significantly associated with poor overall survival (OS) in KIRC, KIRP, LUAD, and UCEC. Amplification was the greatest frequency of the DMRT3 alterations in pan-cancer. The OS was significantly lower in the DMRT3 altered group than in the DMRT3 unaltered group (P = 0.0276). The DMRT3 expression was significantly associated with MSI in three cancer types and TMB in six cancer types. The DMRT3 expression was significantly correlated with the level of the immune cell infiltration and the immune checkpoint genes. The DMRT3 was involved in some pathways in pan-cancer. DMRT3 may play a role in chemotherapy and may be associated with chemoresistance. A ceRNA network of KCNQ1OT1/miR-335-5p/DMRT3 was constructed in LUAD. DMRT3 was significantly upregulated in the LUAD cell lines. DMRT3 was aberrantly expressed in pan-cancer and may promote tumorigenesis and progression via different mechanisms. DMRT3 can be used as a therapeutic target to treat cancer in humans. Full article
►▼ Show Figures

Figure 1

18 pages, 6417 KiB  
Article
GMEB2 Promotes the Growth of Colorectal Cancer by Activating ADRM1 Transcription and NF-κB Signalling and Is Positively Regulated by the m6A Reader YTHDF1
by Zhengping Ning, Zhiwei Wu, Fan Zhang, Ming Yang, Zhixing Lu, Bowen Yu, Fei Long, Yihang Guo, Kaiyan Yang, Gui Hu, Yi Zhang, Xiaorong Li, Liang Li and Changwei Lin
Cancers 2022, 14(24), 6046; https://doi.org/10.3390/cancers14246046 - 8 Dec 2022
Cited by 7 | Viewed by 2078
Abstract
Transcription factors are frequently aberrantly reactivated in various cancers, including colorectal cancer (CRC). However, as a transcription factor, the role of GMEB2 in cancer is still unclear, and further studies are needed. Here, we aimed to identify the function and mechanism of GMEB2 [...] Read more.
Transcription factors are frequently aberrantly reactivated in various cancers, including colorectal cancer (CRC). However, as a transcription factor, the role of GMEB2 in cancer is still unclear, and further studies are needed. Here, we aimed to identify the function and mechanism of GMEB2 in regulating the malignant progression of CRC. GMEB2 was found to be highly expressed in online data analyses. We demonstrated that GMEB2 was markedly upregulated at both the mRNA and protein levels in CRC cells and tissues. GMEB2 knockdown inhibited CRC cell growth in vitro and in vivo. Mechanistically, as a transcription factor, GMEB2 transactivated the ADRM1 promoter to increase its transcription. Rescue experiments showed that ADRM1 downregulation partially reversed the promoting effects of GMEB2 on CRC growth in vitro. Moreover, the GMEB2/ADRM1 axis induced nuclear translocation of NF-κB, thus activating NF-κB signalling. Finally, we further revealed that YTHDF1 recognized and bound to the m6A site on GMEB2 mRNA, which enhanced its stability. Taken together, our findings reveal the crucial role and regulatory mechanism of GMEB2 in CRC for the first time and provide a novel potential therapeutic target for CRC therapy. Full article
►▼ Show Figures

Figure 1

14 pages, 4453 KiB  
Article
An Inflammatory Response-Related Gene Signature Can Predict the Prognosis and Impact the Immune Status of Lung Adenocarcinoma
by Yubo Shi, Yingchun Zhao and Yuanyong Wang
Cancers 2022, 14(23), 5744; https://doi.org/10.3390/cancers14235744 - 23 Nov 2022
Cited by 3 | Viewed by 1839
Abstract
Lung adenocarcinoma (LUAD) accounts for a cancer with high heterogeneity and poor prognostic outcome. Nonetheless, it is still unknown about the relation between inflammatory response-related genes (IRGs) and LUAD. This study used LASSO-Cox regression for establishing the multigene prognostic signature based on TCGA [...] Read more.
Lung adenocarcinoma (LUAD) accounts for a cancer with high heterogeneity and poor prognostic outcome. Nonetheless, it is still unknown about the relation between inflammatory response-related genes (IRGs) and LUAD. This study used LASSO-Cox regression for establishing the multigene prognostic signature based on TCGA and the GSE31210 cohorts. In addition, gene set enrichment analysis (GSEA) was performed for GO and KEGG analyses. By contrast, single-sample GSEA (ssGSEA) investigated immune cell infiltration scores as well as the immune pathway activity. We also conducted qRT-PCR and IHC to evaluate prognostic gene expression at protein and mRNA levels within LUAD and adjacent healthy samples. As a result, a novel prognostic signature involving 10 IRGs was identified. Furthermore, the signature has been validated as being important in functional analysis, TME, drug sensitivity, and prognosis prediction in LUAD. Moreover, prognostic genes showed significant expression at protein and mRNA levels in LUAD compared with normal samples. The signature involving 10 IRGs could potentially predict LUAD prognosis. Full article
►▼ Show Figures

Figure 1

21 pages, 5483 KiB  
Article
Prognosis-Related Molecular Subtypes and Immune Features Associated with Hepatocellular Carcinoma
by Jiazhou Ye, Yan Lin, Xing Gao, Lu Lu, Xi Huang, Shilin Huang, Tao Bai, Guobin Wu, Xiaoling Luo, Yongqiang Li and Rong Liang
Cancers 2022, 14(22), 5721; https://doi.org/10.3390/cancers14225721 - 21 Nov 2022
Cited by 5 | Viewed by 2556
Abstract
Bioinformatics tools were used to identify prognosis-related molecular subtypes and biomarkers of hepatocellular carcinoma (HCC). Differential expression analysis of four datasets identified 3330 overlapping differentially expressed genes (DEGs) in the same direction in all four datasets. Those genes were involved in the cell [...] Read more.
Bioinformatics tools were used to identify prognosis-related molecular subtypes and biomarkers of hepatocellular carcinoma (HCC). Differential expression analysis of four datasets identified 3330 overlapping differentially expressed genes (DEGs) in the same direction in all four datasets. Those genes were involved in the cell cycle, FOXO signaling pathway, as well as complement and coagulation cascades. Based on non-negative matrix decomposition, two molecular subtypes of HCC with different prognoses were identified, with subtype C2 showing better overall survival than subtype C1. Cox regression and Kaplan-Meier analysis showed that 217 of the overlapping DEGs were closely associated with HCC prognosis. The subset of those genes showing an area under the curve >0.80 was used to construct random survival forest and least absolute shrinkage and selection operator models, which identified seven feature genes (SORBS2, DHRS1, SLC16A2, RCL1, IGFALS, GNA14, and FANCI) that may be involved in HCC occurrence and prognosis. Based on the feature genes, risk score and recurrence models were constructed, while a univariate Cox model identified FANCI as a key gene involved mainly in the cell cycle, DNA replication, and mismatch repair. Further analysis showed that FANCI had two mutation sites and that its gene may undergo methylation. Single-sample gene set enrichment analysis showed that Th2 and T helper cells are significantly upregulated in HCC patients compared to controls. Our results identify FANCI as a potential prognostic biomarker for HCC. Full article
►▼ Show Figures

Figure 1

18 pages, 3895 KiB  
Article
Pan-Cancer Analysis Identifies Tumor Cell Surface Targets for CAR-T Cell Therapies and Antibody Drug Conjugates
by Xinhui Li, Jian Zhou, Weiwen Zhang, Wenhua You, Jun Wang, Linlin Zhou, Lei Liu, Wei-Wei Chen and Hanjie Li
Cancers 2022, 14(22), 5674; https://doi.org/10.3390/cancers14225674 - 18 Nov 2022
Cited by 6 | Viewed by 4378
Abstract
Tumor cells can be recognized through tumor surface antigens by immune cells and antibodies, which therefore can be used as drug targets for chimeric antigen receptor-T (CAR-T) therapies and antibody drug conjugates (ADCs). In this study, we aimed to identify novel tumor-specific antigens [...] Read more.
Tumor cells can be recognized through tumor surface antigens by immune cells and antibodies, which therefore can be used as drug targets for chimeric antigen receptor-T (CAR-T) therapies and antibody drug conjugates (ADCs). In this study, we aimed to identify novel tumor-specific antigens as targets for more effective and safer CAR-T cell therapies and ADCs. Here, we performed differential expression analysis of pan-cancer data obtained from the Cancer Genome Atlas (TCGA), and then performed a series of conditional screenings including Cox regression analysis, Pearson correlation analysis, and risk-score calculation to find tumor-specific cell membrane genes. A tumor tissue-specific and highly expressed gene set containing 3919 genes from 17 cancer types was obtained. Moreover, the prognostic roles of these genes and the functions of these highly expressed membrane proteins were assessed. Notably, 427, 584, 431 and 578 genes were identified as risk factors for LIHC, KIRC, UCEC, and KIRP, respectively. Functional enrichment analysis indicated that these tumor-specific surface proteins might confer tumor cells the ability to invade and metastasize. Furthermore, correlation analysis displayed that most overexpressed membrane proteins were positively correlated to each other. In addition, 371 target membrane protein-coding genes were sifted out by excluding proteins expressed in normal tissues. Apart from the identification of well-validated genes such as GPC3, MSLN and EGFR in the literature, we further confirmed the differential protein expression of 23 proteins: ADD2, DEF6, DOK3, ENO2, FMNL1, MICALL2, PARVG, PSTPIP1, FERMT1, PLEK2, CD109, GNG4, MAPT, OSBPL3, PLXNA1, ROBO1, SLC16A3, SLC26A6, SRGAP2, and TMEM65 in four types of tumors. In summary, our findings reveal novel tumor-specific antigens, which could be potentially used for next-generation CAR-T cell therapies and ADC discovery. Full article
►▼ Show Figures

Figure 1

24 pages, 5433 KiB  
Article
Identification of Immunogenic Cell Death-Related Signature for Glioma to Predict Survival and Response to Immunotherapy
by Zhiqiang Sun, Hongxiang Jiang, Tengfeng Yan, Gang Deng and Qianxue Chen
Cancers 2022, 14(22), 5665; https://doi.org/10.3390/cancers14225665 - 18 Nov 2022
Cited by 4 | Viewed by 1962
Abstract
Immunogenic cell death (ICD) is a type of regulated cell death (RCD) and is correlated with the progression, prognosis, and therapy of tumors, including glioma. Numerous studies have shown that the immunotherapeutic and chemotherapeutic agents of glioma might induce ICD. However, studies on [...] Read more.
Immunogenic cell death (ICD) is a type of regulated cell death (RCD) and is correlated with the progression, prognosis, and therapy of tumors, including glioma. Numerous studies have shown that the immunotherapeutic and chemotherapeutic agents of glioma might induce ICD. However, studies on the comprehensive analysis of the role of ICD-related genes and their correlations with overall survival (OS) in glioma are lacking. The genetic, transcriptional, and clinical data of 1896 glioma samples were acquired from five distinct databases and analyzed in terms of genes and transcription levels. The method of consensus unsupervised clustering divided the patients into two disparate molecular clusters: A and B. All of the patients were randomly divided into training and testing groups. Employing the training group data, 14 ICD-related genes were filtered out to develop a risk-score model. The correlations between our risk groups and prognosis, cells in the tumor microenvironment (TME) and immune cells infiltration, chemosensitivity and cancer stem cell (CSC) index were assessed. A highly precise nomogram model was constructed to enhance and optimize the clinical application of the risk score. The results demonstrated that the risk score could independently predict the OS rate and the immunotherapeutic response of glioma patients. This study analyzed the ICD-related genes in glioma and evaluated their role in the OS, clinicopathological characteristics, TME and immune cell infiltration of glioma. Our results may help in assessing the OS of glioma and developing better immunotherapeutic strategies. Full article
►▼ Show Figures

Figure 1

21 pages, 10406 KiB  
Article
Identification of CD73 as a Novel Biomarker Encompassing the Tumor Microenvironment, Prognosis, and Therapeutic Responses in Various Cancers
by Kun Tang, Jingwei Zhang, Hui Cao, Gelei Xiao, Zeyu Wang, Xun Zhang, Nan Zhang, Wantao Wu, Hao Zhang, Qianrong Wang, Huilan Xu and Quan Cheng
Cancers 2022, 14(22), 5663; https://doi.org/10.3390/cancers14225663 - 17 Nov 2022
Cited by 8 | Viewed by 3566
Abstract
CD73 is essential in promoting tumor growth by prohibiting anti-tumor immunity in many cancer types. While the mechanism remains largely unknown, our paper comprehensively confirmed the onco-immunological characteristics of CD73 in the tumor microenvironment (TME) of pan-cancer. This paper explored the expression pattern, [...] Read more.
CD73 is essential in promoting tumor growth by prohibiting anti-tumor immunity in many cancer types. While the mechanism remains largely unknown, our paper comprehensively confirmed the onco-immunological characteristics of CD73 in the tumor microenvironment (TME) of pan-cancer. This paper explored the expression pattern, mutational profile, prognostic value, tumor immune infiltration, and response to immunotherapy of CD73 in a continuous cohort of cancers through various computational tools. The co-expression of CD73 on cancer cells, immune cells, and stromal cells in the TME was also detected. Especially, we examined the correlation between CD73 and CD8+ (a marker of T cell), CD68+ (a marker of macrophage), and CD163+ (a marker of M2 macrophage) cells using multiplex immunofluorescence staining of tissue microarrays. CD73 expression is significantly associated with a patient’s prognosis and could be a promising predictor of these cancers. High CD73 levels are strongly linked to immune infiltrations, neoantigens, and immune checkpoint expression in the TME. In particular, enrichment signaling pathway analysis demonstrated that CD73 was obviously related to activation pathways of immune cells, including T cells, macrophages, and cancer-associated fibroblasts (CAFs). Meanwhile, single-cell sequencing algorithms found that CD73 is predominantly co-expressed on cancer cells, CAFs, M2 macrophages, and T cells in several cancers. In addition, we explored the cellular communication among 14 cell types in glioblastoma (GBM) based on CD73 expression. Based on the expression of CD73 as well as macrophage and T cell markers, we predicted the methylation and enrichment pathways of these markers in pan-cancer. Furthermore, a lot of therapeutic molecules sensitive to these markers were predicted. Finally, potential anticancer inhibitors, immunotherapies, and gene therapy responses targeting CD73 were identified from a series of immunotherapy cohorts. CD73 is closely linked to clinical prognosis and immune infiltration in many cancers. Targeting CD73-dependent signaling pathways may be a promising therapeutic strategy for future tumor immunotherapy. Full article
►▼ Show Figures

Graphical abstract

17 pages, 5938 KiB  
Article
CYP1B1: A Novel Molecular Biomarker Predicts Molecular Subtype, Tumor Microenvironment, and Immune Response in 33 Cancers
by Benchao Yuan, Guihong Liu, Zili Dai, Li Wang, Baisheng Lin and Jian Zhang
Cancers 2022, 14(22), 5641; https://doi.org/10.3390/cancers14225641 - 17 Nov 2022
Cited by 7 | Viewed by 2470
Abstract
Background: Cytochrome P450 Family 1 Subfamily B Member 1 (CYP1B1) is a critical metabolic enzyme of melatonin. Although melatonin has been identified to exhibit tumor suppressing activity, the role and mechanism of the clinical and immunological characteristics of CYP1B1 in cancer remain unclear. [...] Read more.
Background: Cytochrome P450 Family 1 Subfamily B Member 1 (CYP1B1) is a critical metabolic enzyme of melatonin. Although melatonin has been identified to exhibit tumor suppressing activity, the role and mechanism of the clinical and immunological characteristics of CYP1B1 in cancer remain unclear. Methods: In this study, RNA expression and clinical data were obtained from The Cancer Genome Atlas (TCGA) across 33 solid tumors. The expression, survival, immune subtype, molecular subtype, tumor mutation burden (TMB), microsatellite instability (MSI), biological pathways, and function in vitro and vivo were evaluated. The predictive value of CYP1B1 in immune cohorts was further explored. Results: We found the dysregulated expression of CYP1B1 was associated with the clinical stage and tumor grade. Immunological correlation analysis showed CYP1B1 was positively correlated with the infiltration of lymphocyte, immunomodulator, chemokine, receptor, and cancer-associated fibroblasts (CAFs) in most cancer. Meanwhile, CYP1B1 was involved in immune subtype and molecular subtype, and was connected with TMB, MSI, neoantigen, the activation of multiple melatonergic and immune-related pathways, and therapeutic resistance. Conclusions: Together, this study comprehensively revealed the role and mechanism of CYP1B1 and explored the significant association between CYP1B1 expression and immune activity. These findings provide a promising predictor and molecular target for clinical immune treatment. Full article
►▼ Show Figures

Figure 1

29 pages, 13313 KiB  
Article
Construction of a Prognostic and Early Diagnosis Model for LUAD Based on Necroptosis Gene Signature and Exploration of Immunotherapy Potential
by Baizhuo Zhang, Yudong Wang, Xiaozhu Zhou, Zhen Zhang, Haoyu Ju, Xiaoqi Diao, Jiaoqi Wu and Jing Zhang
Cancers 2022, 14(20), 5153; https://doi.org/10.3390/cancers14205153 - 20 Oct 2022
Cited by 3 | Viewed by 2475
Abstract
Necroptosis is a type of programmed necrosis that is different from apoptosis and necrosis. Lung cancer has the highest incidence and mortality worldwide, and lung adenocarcinoma is the most common subtype of lung cancer. However, the role of necroptosis in the occurrence and [...] Read more.
Necroptosis is a type of programmed necrosis that is different from apoptosis and necrosis. Lung cancer has the highest incidence and mortality worldwide, and lung adenocarcinoma is the most common subtype of lung cancer. However, the role of necroptosis in the occurrence and development of LUAD remains largely unexplored. In this paper, four NRGs and nine NRGs determined by big data analysis were used to effectively predict the risk of early LUAD (AUC = 0.994) and evaluate the prognostic effect on LUAD patients (AUC = 0.826). Meanwhile, ESTIMATE, single-sample gene set enrichment analysis (ssGSEA), genomic variation analysis (GSVA), gene set enrichment analysis (GSEA), and immune checkpoint analysis were used to explore the enrichment characteristics and immune research related to the prognostic model. In deep data mining, we were surprised to find that prognostic models also regulate the immune microenvironment, cell cycle, and DNA damage repair mechanisms. Thus, we demonstrated a significant correlation between model evaluation results, ICI treatment, and chemotherapeutic drug sensitivity. The low-risk population has a stronger tumor immune response, and the potential for ICI treatment is greater. People at high risk respond less to immunotherapy but respond well to chemotherapy drugs. In addition, PANX1, a core gene with important value in immune regulation, prognosis assessment, and early diagnosis, has been identified for the first time, which provides a new target for the immunotherapy of LUAD as well as a new theoretical basis for the basic research, clinical diagnosis, and individualized treatment of LUAD. Full article
►▼ Show Figures

Figure 1

19 pages, 26827 KiB  
Article
Pan-Cancer Analysis and Experimental Validation Identify ACOT7 as a Novel Oncogene and Potential Therapeutic Target in Lung Adenocarcinoma
by Chao Zheng, Guochao Zhang, Kai Xie, Yifei Diao, Chao Luo, Yanqing Wang, Yi Shen and Qi Xue
Cancers 2022, 14(18), 4522; https://doi.org/10.3390/cancers14184522 - 18 Sep 2022
Cited by 2 | Viewed by 3331
Abstract
Background: Acyl-CoA thioesterase 7 (ACOT7) is of great significance in regulating cell cycle, cell proliferation, and glucose metabolism. The function of ACOT7 in pan-cancer and its capacity as a prognostic indicator in lung adenocarcinoma (LUAD) remains unknown. We intended to perform a comprehensive [...] Read more.
Background: Acyl-CoA thioesterase 7 (ACOT7) is of great significance in regulating cell cycle, cell proliferation, and glucose metabolism. The function of ACOT7 in pan-cancer and its capacity as a prognostic indicator in lung adenocarcinoma (LUAD) remains unknown. We intended to perform a comprehensive pan-cancer analysis of ACOT7 and to validate its value in LUAD. Methods: The expression levels, prognostic significance, molecular function, signaling pathways, and immune infiltration pattern of ACOT7 in 33 cancers were explored via systematic bioinformatics analysis. Multivariate Cox regression was applied to construct nomograms to predict patients’ prognoses. Moreover, we conducted in vitro experiments including CCK8, scratch, Transwell, and Matrigel assays to further explore the function of ACOT7 in LUAD. Results: Patients with high ACOT7 expression have notably poorer long-term survival in many cancer types, including LUAD. Further enrichment analyses reveal that ACOT7 is involved in immune cells’ infiltration and is substantially related to the cancer–immune microenvironment. ACOT7 could influence drug sensitivities, including afatinib, gefitinib, ibrutinib, lapatinib, osimertinib, sapitinib, taselisib, and PLX-4720 (all p < 0.01). A nomogram demonstrated a fair predictive value of ACOT7 in LUAD (C-index: 0.613, 95% CI: 0.568–0.658). The proliferation and migration of PC9 cells were significantly repressed when ACOT7 expression was downregulated. Conclusion: As an oncogene, ACOT7 is critical in the tumor microenvironment of pan-cancer and might be a novel therapeutic target for LUAD. Full article
►▼ Show Figures

Figure 1

20 pages, 5251 KiB  
Article
Crosstalk of Oxidative Phosphorylation-Related Subtypes, Establishment of a Prognostic Signature and Immune Infiltration Characteristics in Colorectal Adenocarcinoma
by Can Wang, Guoliang Cui, Dan Wang, Min Wang, Qi Chen, Yunshan Wang, Mengjie Lu, Xinyi Tang and Bolin Yang
Cancers 2022, 14(18), 4503; https://doi.org/10.3390/cancers14184503 - 16 Sep 2022
Cited by 5 | Viewed by 2347
Abstract
Oxidative phosphorylation (OXPHOS) is an emerging target in cancer therapy. However, the prognostic signature of OXPHOS in colorectal adenocarcinoma (COAD) remains non-existent. We comprehensively investigated the expression pattern of OXPHOS-related genes (ORGs) in COAD from public databases. Based on four ORGs, an OXPHOS-related [...] Read more.
Oxidative phosphorylation (OXPHOS) is an emerging target in cancer therapy. However, the prognostic signature of OXPHOS in colorectal adenocarcinoma (COAD) remains non-existent. We comprehensively investigated the expression pattern of OXPHOS-related genes (ORGs) in COAD from public databases. Based on four ORGs, an OXPHOS-related prognostic signature was established in which COAD patients were assigned different risk scores and classified into two different risk groups. It was observed that the low-risk group had a better prognosis but lower immune activities including immune cells and immune-related function in the tumor microenvironment. Combining with relevant clinical features, a nomogram for clinical application was also established. Receiver operating characteristic (ROC) and calibration curves were constructed to demonstrate the predictive ability of this risk signature. Moreover, a higher risk score was significantly positively correlated with higher tumor mutation burden (TMB) and generally higher gene expression of immune checkpoint, N6-methyladenosine (m6A) RNA methylation regulators and mismatch repair (MMR) related proteins. The results also indicated that the high-risk group was more sensitive to immunotherapy and certain chemotherapy drugs. In conclusion, OXPHOS-related prognostic signature can be utilized to better understand the roles of ORGs and offer new perspectives for clinical prognosis and personalized treatment. Full article
►▼ Show Figures

Figure 1

17 pages, 5713 KiB  
Article
Single-Cell Profiling of the Immune Atlas of Tumor-Infiltrating Lymphocytes in Endometrial Carcinoma
by Fang Jiang, Yuhao Jiao, Kun Yang, Mingyi Mao, Mei Yu, Dongyan Cao and Yang Xiang
Cancers 2022, 14(17), 4311; https://doi.org/10.3390/cancers14174311 - 2 Sep 2022
Cited by 6 | Viewed by 2748
Abstract
Endometrial carcinoma (EC) is a gynecological malignancy with a high incidence; however, thorough studies on tumor-infiltrating lymphocyte (TIL) populations in EC are lacking. We aimed to map the immune atlas of TILs in type I EC via single-cell RNA sequencing (scRNA-seq), mass cytometry [...] Read more.
Endometrial carcinoma (EC) is a gynecological malignancy with a high incidence; however, thorough studies on tumor-infiltrating lymphocyte (TIL) populations in EC are lacking. We aimed to map the immune atlas of TILs in type I EC via single-cell RNA sequencing (scRNA-seq), mass cytometry and flow cytometry analysis. We found that natural killer (NK) cells and CD8+ T lymphocytes were the major components of TILs in EC patients. We first identified three transcriptionally distinct NK cell subsets, which are likely to possess diverse anti-tumor functions. Additionally, CD103+ cells substantially contributed to the CD8+ T cell population. The signature gene expression of CD103+ CD8+ T cells indicated the tissue residency, immunological memory, and exhaustion properties of this cell subset, which were defined as tissue-resident memory T cells (TRM cells). Moreover, based on scRNA-seq and mass cytometry analysis, we first identified the intrinsic heterogeneity of CD103+ CD8+ T cells that were thought to have a distinct cytotoxicity, cell adhesion and exhaustion status functions. Collectively, distinct subsets of NK cells were found and might shed light on future investigations. CD103+ CD8+ T cell population may be an important immunotherapeutic target in EC and targeting this cell population with combined immunosuppressive therapy might improve the efficacy of immunotherapy for EC. Full article
►▼ Show Figures

Figure 1

22 pages, 12839 KiB  
Article
The m6A-Related Long Noncoding RNA Signature Predicts Prognosis and Indicates Tumor Immune Infiltration in Ovarian Cancer
by Rui Geng, Tian Chen, Zihang Zhong, Senmiao Ni, Jianling Bai and Jinhui Liu
Cancers 2022, 14(16), 4056; https://doi.org/10.3390/cancers14164056 - 22 Aug 2022
Cited by 11 | Viewed by 3079
Abstract
Background: OV is the most lethal gynecological malignancy. M6A and lncRNAs have a great impact on OV development and patient immunotherapy response. In this paper, we decided to establish a reliable signature of mRLs. Method: The lncRNAs associated with m6A in OV were [...] Read more.
Background: OV is the most lethal gynecological malignancy. M6A and lncRNAs have a great impact on OV development and patient immunotherapy response. In this paper, we decided to establish a reliable signature of mRLs. Method: The lncRNAs associated with m6A in OV were analyzed and obtained by co-expression analysis of the TCGA-OV database. Univariate, LASSO and multivariate Cox regression analyses were employed to establish the model of mRLs. K-M analysis, PCA, GSEA and nomogram based on the TCGA-OV and GEO database were conducted to prove the predictive value and independence of the model. The underlying relationship between the model and TME and cancer stemness properties were further investigated through immune feature comparison, consensus clustering analysis and pan-cancer analysis. Results: A prognostic signature comprising four mRLs, WAC-AS1, LINC00997, DNM3OS and FOXN3-AS1, was constructed and verified for OV according to the TCGA and GEO database. The expressions of the four mRLs were confirmed by qRT-PCR in clinical samples. Applying this signature, one can identify patients more effectively. The samples were divided into two clusters, and the clusters had different overall survival rates, clinical features and tumor microenvironments. Finally, pan-cancer analysis further demonstrated that the four mRLs were significantly related to immune infiltration, TME and cancer stemness properties in various cancer types. Conclusions: This study provided an accurate prognostic signature for patients with OV and elucidated the potential mechanism of the mRLs in immune modulation and treatment response, giving new insights into identifying new therapeutic targets. Full article
►▼ Show Figures

Figure 1

18 pages, 4298 KiB  
Article
Identification of a Novel Cuproptosis-Related Gene Signature for Prognostic Implication in Head and Neck Squamous Carcinomas
by Shouyi Tang, Li Zhao, Xing-Bo Wu, Zhen Wang, Lu-Yao Cai, Dan Pan, Ying Li, Yu Zhou and Yingqiang Shen
Cancers 2022, 14(16), 3986; https://doi.org/10.3390/cancers14163986 - 18 Aug 2022
Cited by 25 | Viewed by 5098
Abstract
Head and neck squamous carcinoma (HNSC) is a frequent and deadly malignancy that is challenging to manage. The existing treatment options have considerable efficacy limitations. Hence, the identification of new therapeutic targets and the development of efficacious treatments are urgent needs. Cuproptosis, a [...] Read more.
Head and neck squamous carcinoma (HNSC) is a frequent and deadly malignancy that is challenging to manage. The existing treatment options have considerable efficacy limitations. Hence, the identification of new therapeutic targets and the development of efficacious treatments are urgent needs. Cuproptosis, a non-apoptotic programmed cell death caused by excess copper, has only very recently been discovered. The present study investigated the prognostic importance of genes involved in cuproptosis through the mRNA expression data and related clinical information of HNSC patients downloaded from public databases. Our results revealed that many cuproptosis-related genes were differentially expressed between normal and HNSC tissues in the TCGA cohort. Moreover, 39 differentially expressed genes were associated with the prognosis of HNSC patients. Then, a 24-gene signature was identified in the TCGA cohort utilizing the LASSO Cox regression model. HNSC expression data used for validation were obtained from the GEO database. Consequently, we divided patients into high- and low-risk groups based on the 24-gene signature. Furthermore, we demonstrated that the high-risk group had a worse prognosis when compared to the low-risk group. Additionally, significant differences were found between the two groups in metabolic pathways, immune microenvironment, etc. In conclusion, we found a cuproptosis-related gene signature that can be used effectively to predict OS in HNSC patients. Thus, targeting cuproptosis might be an alternative and promising strategy for HNSC patients. Full article
►▼ Show Figures

Figure 1

14 pages, 2560 KiB  
Article
Identification of Prognostic Genes in Gliomas Based on Increased Microenvironment Stiffness
by Chaang-Ray Chen, Rong-Shing Chang and Chi-Shuo Chen
Cancers 2022, 14(15), 3659; https://doi.org/10.3390/cancers14153659 - 27 Jul 2022
Cited by 4 | Viewed by 2589
Abstract
With a median survival time of 15 months, glioblastoma multiforme is one of the most aggressive primary brain cancers. The crucial roles played by the extracellular matrix (ECM) stiffness in glioma progression and treatment resistance have been reported in numerous studies. However, the [...] Read more.
With a median survival time of 15 months, glioblastoma multiforme is one of the most aggressive primary brain cancers. The crucial roles played by the extracellular matrix (ECM) stiffness in glioma progression and treatment resistance have been reported in numerous studies. However, the association between ECM-stiffness-regulated genes and the prognosis of glioma patients remains to be explored. Thus, using bioinformatics analysis, we first identified 180 stiffness-dependent genes from an RNA-Seq dataset, and then evaluated their prognosis in The Cancer Genome Atlas (TCGA) glioma dataset. Our results showed that 11 stiffness-dependent genes common between low- and high-grade gliomas were prognostic. After validation using the Chinese Glioma Genome Atlas (CGGA) database, we further identified four stiffness-dependent prognostic genes: FN1, ITGA5, OSMR, and NGFR. In addition to high-grade glioma, overexpression of the four-gene signature also showed poor prognosis in low-grade glioma patients. Moreover, our analysis confirmed that the expression levels of stiffness-dependent prognostic genes in high-grade glioma were significantly higher than in low-grade glioma, suggesting that these genes were associated with glioma progression. Based on a pathophysiology-inspired approach, our findings illuminate the link between ECM stiffness and the prognosis of glioma patients and suggest a signature of four stiffness-dependent genes as potential therapeutic targets. Full article
►▼ Show Figures

Figure 1

14 pages, 958 KiB  
Article
Cancer Metabolic Subtypes and Their Association with Molecular and Clinical Features
by Enrico Moiso and Paolo Provero
Cancers 2022, 14(9), 2145; https://doi.org/10.3390/cancers14092145 - 25 Apr 2022
Cited by 3 | Viewed by 2220
Abstract
The alterations of metabolic pathways in cancer have been investigated for many years, beginning long before the discovery of the role of oncogenes and tumor suppressors, and the last few years have witnessed renewed interest in this topic. Large-scale molecular and clinical data [...] Read more.
The alterations of metabolic pathways in cancer have been investigated for many years, beginning long before the discovery of the role of oncogenes and tumor suppressors, and the last few years have witnessed renewed interest in this topic. Large-scale molecular and clinical data on tens of thousands of samples allow us to tackle the problem from a general point of view. Here, we show that transcriptomic profiles of tumors can be exploited to define metabolic cancer subtypes, which can be systematically investigated for associations with other molecular and clinical data. We find thousands of significant associations between metabolic subtypes and molecular features such as somatic mutations, structural variants, epigenetic modifications, protein abundance and activation, and with clinical/phenotypic data, including survival probability, tumor grade, and histological types, which we make available to the community in a dedicated web resource. Our work provides a methodological framework and a rich database of statistical associations, which will contribute to the understanding of the role of metabolic alterations in cancer and to the development of precision therapeutic strategies. Full article
►▼ Show Figures

Figure 1

16 pages, 2778 KiB  
Article
Radiomic Phenotypes for Improving Early Prediction of Survival in Stage III Non-Small Cell Lung Cancer Adenocarcinoma after Chemoradiation
by José Marcio Luna, Andrew R. Barsky, Russell T. Shinohara, Leonid Roshkovan, Michelle Hershman, Alexandra D. Dreyfuss, Hannah Horng, Carolyn Lou, Peter B. Noël, Keith A. Cengel, Sharyn Katz, Eric S. Diffenderfer and Despina Kontos
Cancers 2022, 14(3), 700; https://doi.org/10.3390/cancers14030700 - 29 Jan 2022
Cited by 8 | Viewed by 5366
Abstract
We evaluate radiomic phenotypes derived from CT scans as early predictors of overall survival (OS) after chemoradiation in stage III primary lung adenocarcinoma. We retrospectively analyzed 110 thoracic CT scans acquired between April 2012−October 2018. Patients received a median radiation dose of 66.6 [...] Read more.
We evaluate radiomic phenotypes derived from CT scans as early predictors of overall survival (OS) after chemoradiation in stage III primary lung adenocarcinoma. We retrospectively analyzed 110 thoracic CT scans acquired between April 2012−October 2018. Patients received a median radiation dose of 66.6 Gy at 1.8 Gy/fraction delivered with proton (55.5%) and photon (44.5%) beam treatment, as well as concurrent chemotherapy (89%) with carboplatin-based (55.5%) and cisplatin-based (36.4%) doublets. A total of 56 death events were recorded. Using manual tumor segmentations, 107 radiomic features were extracted. Feature harmonization using ComBat was performed to mitigate image heterogeneity due to the presence or lack of intravenous contrast material and variability in CT scanner vendors. A binary radiomic phenotype to predict OS was derived through the unsupervised hierarchical clustering of the first principal components explaining 85% of the variance of the radiomic features. C-scores and likelihood ratio tests (LRT) were used to compare the performance of a baseline Cox model based on ECOG status and age, with a model integrating the radiomic phenotype with such clinical predictors. The model integrating the radiomic phenotype (C-score = 0.69, 95% CI = (0.62, 0.77)) significantly improved (p<0.005) upon the baseline model (C-score = 0.65, CI = (0.57, 0.73)). Our results suggest that harmonized radiomic phenotypes can significantly improve OS prediction in stage III NSCLC after chemoradiation. Full article
►▼ Show Figures

Figure 1

2021

Jump to: 2024, 2023, 2022, 2020, 2019

12 pages, 2684 KiB  
Article
PPAR-Responsive Elements Enriched with Alu Repeats May Contribute to Distinctive PPARγ–DNMT1 Interactions in the Genome
by Amit Sharma, Fabian Tobar-Tosse, Tikam Chand Dakal, Hongde Liu, Arijit Biswas, Athira Menon, Anoosha Paruchuri, Panagiotis Katsonis, Olivier Lichtarge, M. Michael Gromiha, Michael Ludwig, Ingo G. H. Schmidt-Wolf, Frank G. Holz, Karin U. Loeffler and Martina C. Herwig-Carl
Cancers 2021, 13(16), 3993; https://doi.org/10.3390/cancers13163993 - 7 Aug 2021
Cited by 3 | Viewed by 3061
Abstract
Background: PPARγ (peroxisome proliferator-activated receptor gamma) is involved in the pathology of numerous diseases, including UM and other types of cancer. Emerging evidence suggests that an interaction between PPARγ and DNMTs (DNA methyltransferase) plays a role in cancer that is yet to be [...] Read more.
Background: PPARγ (peroxisome proliferator-activated receptor gamma) is involved in the pathology of numerous diseases, including UM and other types of cancer. Emerging evidence suggests that an interaction between PPARγ and DNMTs (DNA methyltransferase) plays a role in cancer that is yet to be defined. Methods: The configuration of the repeating elements was performed with CAP3 and MAFFT, and the structural modelling was conducted with HDOCK. An evolutionary action scores algorithm was used to identify oncogenic variants. A systematic bioinformatic appraisal of PPARγ and DNMT1 was performed across 29 tumor types and UM available in The Cancer Genome Atlas (TCGA). Results: PPAR-responsive elements (PPREs) enriched with Alu repeats are associated with different genomic regions, particularly the promotor region of DNMT1. PPARγ–DNMT1 co-expression is significantly associated with several cancers. C-terminals of PPARγ and DNMT1 appear to be the potential protein–protein interaction sites where disease-specific mutations may directly impair the respective protein functions. Furthermore, PPARγ expression could be identified as an additional prognostic marker for UM. Conclusions: We hypothesize that the function of PPARγ requires an additional contribution of Alu repeats which may directly influence the DNMT1 network. Regarding UM, PPARγ appears to be an additional discriminatory prognostic marker, in particular in disomy 3 tumors. Full article
►▼ Show Figures

Figure 1

25 pages, 3257 KiB  
Review
Target Heterogeneity in Oncology: The Best Predictor for Differential Response to Radioligand Therapy in Neuroendocrine Tumors and Prostate Cancer
by Ameya D Puranik, Clarisse Dromain, Neil Fleshner, Mike Sathekge, Marianne Pavel, Nina Eberhardt, Friedemann Zengerling, Ralf Marienfeld, Michael Grunert and Vikas Prasad
Cancers 2021, 13(14), 3607; https://doi.org/10.3390/cancers13143607 - 19 Jul 2021
Cited by 15 | Viewed by 4473
Abstract
Tumor or target heterogeneity (TH) implies presence of variable cellular populations having different genomic characteristics within the same tumor, or in different tumor sites of the same patient. The challenge is to identify this heterogeneity, as it has emerged as the most common [...] Read more.
Tumor or target heterogeneity (TH) implies presence of variable cellular populations having different genomic characteristics within the same tumor, or in different tumor sites of the same patient. The challenge is to identify this heterogeneity, as it has emerged as the most common cause of ‘treatment resistance’, to current therapeutic agents. We have focused our discussion on ‘Prostate Cancer’ and ‘Neuroendocrine Tumors’, and looked at the established methods for demonstrating heterogeneity, each with its advantages and drawbacks. Also, the available theranostic radiotracers targeting PSMA and somatostatin receptors combined with targeted systemic agents, have been described. Lu-177 labeled PSMA and DOTATATE are the ‘standard of care’ radionuclide therapeutic tracers for management of progressive treatment-resistant prostate cancer and NET. These approved therapies have shown reasonable benefit in treatment outcome, with improvement in quality of life parameters. Various biomarkers and predictors of response to radionuclide therapies targeting TH which are currently available and those which can be explored have been elaborated in details. Imaging-based features using artificial intelligence (AI) need to be developed to further predict the presence of TH. Also, novel theranostic tools binding to newer targets on surface of cancer cell should be explored to overcome the treatment resistance to current treatment regimens. Full article
►▼ Show Figures

Figure 1

20 pages, 3537 KiB  
Article
NF-Y Subunits Overexpression in HNSCC
by Eugenia Bezzecchi, Andrea Bernardini, Mirko Ronzio, Claudia Miccolo, Susanna Chiocca, Diletta Dolfini and Roberto Mantovani
Cancers 2021, 13(12), 3019; https://doi.org/10.3390/cancers13123019 - 16 Jun 2021
Cited by 10 | Viewed by 3700
Abstract
NF-Y is the CCAAT-binding trimer formed by the histone fold domain (HFD), NF-YB/NF-YC and NF-YA. The CCAAT box is generally prevalent in promoters of “cancer” genes. We reported the overexpression of NF-YA in BRCA, LUAD and LUSC, and of all subunits in HCC. [...] Read more.
NF-Y is the CCAAT-binding trimer formed by the histone fold domain (HFD), NF-YB/NF-YC and NF-YA. The CCAAT box is generally prevalent in promoters of “cancer” genes. We reported the overexpression of NF-YA in BRCA, LUAD and LUSC, and of all subunits in HCC. Altered splicing of NF-YA was found in breast and lung cancer. We analyzed RNA-seq datasets of TCGA and cell lines of head and neck squamous cell carcinomas (HNSCC). We partitioned all TCGA data into four subtypes, deconvoluted single-cell RNA-seq of tumors and derived survival curves. The CCAAT box was enriched in the promoters of overexpressed genes. The “short” NF-YAs was overexpressed in all subtypes and the “long” NF-YAl in Mesenchymal. The HFD subunits are overexpressed, except Basal (NF-YB) and Atypical (NF-YC); NF-YAl is increased in p53 mutated tumors. In HPV-positive tumors, high levels of NF-YAs, p16 and ΔNp63 correlate with better prognosis. Deconvolution of single cell RNA-seq (scRNA-seq) found a correlation of NF-YAl with Cancer Associated Fibroblasts (CAFs) and p-EMT cells, a population endowed with metastatic potential. We conclude that overexpression of HFD subunits and NF-YAs is protective in HPV-positive tumors; expression of NF-YAl is largely confined to mutp53 tumors and malignant p-EMT cells. Full article
►▼ Show Figures

Figure 1

20 pages, 1947 KiB  
Article
Evolutionary Trajectories and Genomic Divergence in Localized Breast Cancers after Ipsilateral Breast Tumor Recurrence
by Chia-Hsin Wu, Hsien-Tang Yeh, Chia-Shan Hsieh, Chi-Cheng Huang, Amrita Chattopadhyay, Yuan-Chiang Chung, Shih-Hsin Tu, Yung-Hua Li, Tzu-Pin Lu, Liang-Chuan Lai, Ming-Feng Hou, King-Jen Chang, Mong-Hsun Tsai and Eric Y. Chuang
Cancers 2021, 13(8), 1821; https://doi.org/10.3390/cancers13081821 - 11 Apr 2021
Cited by 3 | Viewed by 2919
Abstract
The evolutionary trajectories that drive clinical and therapeutic consequences in localized breast cancers (BCs) with ipsilateral breast tumor relapse (IBTR) remain largely unknown. Analyses of longitudinal paired whole-exome sequencing data from 10 localized BC patients with IBTR reveal that, compared to primary breast [...] Read more.
The evolutionary trajectories that drive clinical and therapeutic consequences in localized breast cancers (BCs) with ipsilateral breast tumor relapse (IBTR) remain largely unknown. Analyses of longitudinal paired whole-exome sequencing data from 10 localized BC patients with IBTR reveal that, compared to primary breast tumors, homologous recombination (HR) deficiency, inactivation of the HR pathway, chromosomal instability, and somatic driver mutations are more frequent. Furthermore, three major models of evolution in IBTR are summarized, through which relative contributions of mutational signatures shift, and the subclonal diversity expansions are shown. Optimal treatment regimens are suggested by the clinically relevant molecular features, such as HR deficiency (20%) or specific alterations (30%) with sensitivity to available FDA-approved drugs. Finally, a rationale for the development of the therapeutic management framework is provided. This study sheds light on the complicated evolution patterns in IBTR and has significant clinical implications for future improvement of treatment decisions. Full article
►▼ Show Figures

Figure 1

12 pages, 518 KiB  
Review
Bioinformatic Approaches to Validation and Functional Analysis of 3D Lung Cancer Models
by P. Jonathan Li, Jeroen P. Roose, David M. Jablons and Johannes R. Kratz
Cancers 2021, 13(4), 701; https://doi.org/10.3390/cancers13040701 - 9 Feb 2021
Cited by 3 | Viewed by 3894
Abstract
3D models of cancer have the potential to improve basic, translational, and clinical studies. Patient-derived xenografts, spheroids, and organoids are broad categories of 3D models of cancer, and to date, these 3D models of cancer have been established for a variety of cancer [...] Read more.
3D models of cancer have the potential to improve basic, translational, and clinical studies. Patient-derived xenografts, spheroids, and organoids are broad categories of 3D models of cancer, and to date, these 3D models of cancer have been established for a variety of cancer types. In lung cancer, for example, 3D models offer a promising new avenue to gain novel insights into lung tumor biology and improve outcomes for patients afflicted with the number one cancer killer worldwide. However, the adoption and utility of these 3D models of cancer vary, and demonstrating the fidelity of these models is a critical first step before seeking meaningful applications. Here, we review use cases of current 3D lung cancer models and bioinformatic approaches to assessing model fidelity. Bioinformatics approaches play a key role in both validating 3D lung cancer models and high dimensional functional analyses to support downstream applications. Full article
►▼ Show Figures

Figure 1

26 pages, 5538 KiB  
Article
Cancers in Agreement? Exploring the Cross-Talk of Cancer Metabolomic and Transcriptomic Landscapes Using Publicly Available Data
by Derek van Tilborg and Edoardo Saccenti
Cancers 2021, 13(3), 393; https://doi.org/10.3390/cancers13030393 - 21 Jan 2021
Cited by 3 | Viewed by 3320
Abstract
One of the major hallmarks of cancer is the derailment of a cell’s metabolism. The multifaceted nature of cancer and different cancer types is transduced by both its transcriptomic and metabolomic landscapes. In this study, we re-purposed the publicly available transcriptomic and metabolomics [...] Read more.
One of the major hallmarks of cancer is the derailment of a cell’s metabolism. The multifaceted nature of cancer and different cancer types is transduced by both its transcriptomic and metabolomic landscapes. In this study, we re-purposed the publicly available transcriptomic and metabolomics data of eight cancer types (breast, lung, gastric, renal, liver, colorectal, prostate, and multiple myeloma) to find and investigate differences and commonalities on a pathway level among different cancer types. Topological analysis of inferred graphical Gaussian association networks showed that cancer was strongly defined in genetic networks, but not in metabolic networks. Using different statistical approaches to find significant differences between cancer and control cases, we highlighted the difficulties of high-level data-merging and in using statistical association networks. Cancer transcriptomics and metabolomics and landscapes were characterized by changed macro-molecule production, however, only major metabolic deregulations with highly impacted pathways were found in liver cancer. Cell cycle was enriched in breast, liver, and colorectal cancer, while breast and lung cancer were distinguished by highly enriched oncogene signaling pathways. A strong inflammatory response was observed in lung cancer and, to some extent, renal cancer. This study highlights the necessity of combining different omics levels to obtain a better description of cancer characteristics. Full article
►▼ Show Figures

Figure 1

24 pages, 7171 KiB  
Article
The Transcriptomic Landscape of Prostate Cancer Development and Progression: An Integrative Analysis
by Jacek Marzec, Helen Ross-Adams, Stefano Pirrò, Jun Wang, Yanan Zhu, Xueying Mao, Emanuela Gadaleta, Amar S. Ahmad, Bernard V. North, Solène-Florence Kammerer-Jacquet, Elzbieta Stankiewicz, Sakunthala C. Kudahetti, Luis Beltran, Guoping Ren, Daniel M. Berney, Yong-Jie Lu and Claude Chelala
Cancers 2021, 13(2), 345; https://doi.org/10.3390/cancers13020345 - 19 Jan 2021
Cited by 8 | Viewed by 3875
Abstract
Next-generation sequencing of primary tumors is now standard for transcriptomic studies, but microarray-based data still constitute the majority of available information on other clinically valuable samples, including archive material. Using prostate cancer (PC) as a model, we developed a robust analytical framework to [...] Read more.
Next-generation sequencing of primary tumors is now standard for transcriptomic studies, but microarray-based data still constitute the majority of available information on other clinically valuable samples, including archive material. Using prostate cancer (PC) as a model, we developed a robust analytical framework to integrate data across different technical platforms and disease subtypes to connect distinct disease stages and reveal potentially relevant genes not identifiable from single studies alone. We reconstructed the molecular profile of PC to yield the first comprehensive insight into its development, by tracking changes in mRNA levels from normal prostate to high-grade prostatic intraepithelial neoplasia, and metastatic disease. A total of nine previously unreported stage-specific candidate genes with prognostic significance were also found. Here, we integrate gene expression data from disparate sample types, disease stages and technical platforms into one coherent whole, to give a global view of the expression changes associated with the development and progression of PC from normal tissue through to metastatic disease. Summary and individual data are available online at the Prostate Integrative Expression Database (PIXdb), a user-friendly interface designed for clinicians and laboratory researchers to facilitate translational research. Full article
►▼ Show Figures

Figure 1

2020

Jump to: 2024, 2023, 2022, 2021, 2019

16 pages, 3902 KiB  
Article
Tumors Widely Express Hundreds of Embryonic Germline Genes
by Jan Willem Bruggeman, Naoko Irie, Paul Lodder, Ans M. M. van Pelt, Jan Koster and Geert Hamer
Cancers 2020, 12(12), 3812; https://doi.org/10.3390/cancers12123812 - 17 Dec 2020
Cited by 12 | Viewed by 3730
Abstract
We have recently described a class of 756 genes that are widely expressed in cancers, but are normally restricted to adult germ cells, referred to as germ cell cancer genes (GC genes). We hypothesized that carcinogenesis involves the reactivation of biomolecular processes and [...] Read more.
We have recently described a class of 756 genes that are widely expressed in cancers, but are normally restricted to adult germ cells, referred to as germ cell cancer genes (GC genes). We hypothesized that carcinogenesis involves the reactivation of biomolecular processes and regulatory mechanisms that, under normal circumstances, are restricted to germline development. This would imply that cancer cells share gene expression profiles with primordial germ cells (PGCs). We therefore compared the transcriptomes of human PGCs (hPGCs) and PGC-like cells (PGCLCs) with 17,382 samples from 54 healthy somatic tissues (GTEx) and 11,003 samples from 33 tumor types (TCGA), and identified 672 GC genes, expanding the known GC gene pool by 387 genes (51%). We found that GC genes are expressed in clusters that are often expressed in multiple tumor types. Moreover, the amount of GC gene expression correlates with poor survival in patients with lung adenocarcinoma. As GC genes specific to the embryonic germline are not expressed in any adult tissue, targeting these in cancer treatment may result in fewer side effects than targeting conventional cancer/testis (CT) or GC genes and may preserve fertility. We anticipate that our extended GC dataset enables improved understanding of tumor development and may provide multiple novel targets for cancer treatment development. Full article
►▼ Show Figures

Figure 1

17 pages, 4747 KiB  
Article
Unsupervised Hierarchical Clustering of Pancreatic Adenocarcinoma Dataset from TCGA Defines a Mucin Expression Profile that Impacts Overall Survival
by Nicolas Jonckheere, Julie Auwercx, Elsa Hadj Bachir, Lucie Coppin, Nihad Boukrout, Audrey Vincent, Bernadette Neve, Mathieu Gautier, Victor Treviño and Isabelle Van Seuningen
Cancers 2020, 12(11), 3309; https://doi.org/10.3390/cancers12113309 - 9 Nov 2020
Cited by 19 | Viewed by 4981
Abstract
Mucins are commonly associated with pancreatic ductal adenocarcinoma (PDAC) that is a deadly disease because of the lack of early diagnosis and efficient therapies. There are 22 mucin genes encoding large O-glycoproteins divided into two major subgroups: membrane-bound and secreted mucins. We [...] Read more.
Mucins are commonly associated with pancreatic ductal adenocarcinoma (PDAC) that is a deadly disease because of the lack of early diagnosis and efficient therapies. There are 22 mucin genes encoding large O-glycoproteins divided into two major subgroups: membrane-bound and secreted mucins. We investigated mucin expression and their impact on patient survival in the PDAC dataset from The Cancer Genome Atlas (PAAD-TCGA). We observed a statistically significant increased messenger RNA (mRNA) relative level of most of the membrane-bound mucins (MUC1/3A/4/12/13/16/17/20), secreted mucins (MUC5AC/5B), and atypical mucins (MUC14/18) compared to normal pancreas. We show that MUC1/4/5B/14/17/20/21 mRNA levels are associated with poorer survival in the high-expression group compared to the low-expression group. Using unsupervised clustering analysis of mucin gene expression patterns, we identified two major clusters of patients. Cluster #1 harbors a higher expression of MUC15 and atypical MUC14/MUC18, whereas cluster #2 is characterized by a global overexpression of membrane-bound mucins (MUC1/4/16/17/20/21). Cluster #2 is associated with shorter overall survival. The patient stratification appears to be independent of usual clinical features (tumor stage, differentiation grade, lymph node invasion) suggesting that the pattern of membrane-bound mucin expression could be a new prognostic marker for PDAC patients. Full article
►▼ Show Figures

Figure 1

13 pages, 2079 KiB  
Article
Analysis of Cross-Association between mRNA Expression and RNAi Efficacy for Predictive Target Discovery in Colon Cancers
by Euna Jeong, Yejin Lee, Youngju Kim, Jieun Lee and Sukjoon Yoon
Cancers 2020, 12(11), 3091; https://doi.org/10.3390/cancers12113091 - 23 Oct 2020
Cited by 13 | Viewed by 2577
Abstract
The availability of large-scale, collateral mRNA expression and RNAi data from diverse cancer cell types provides useful resources for the discovery of anticancer targets for which inhibitory efficacy can be predicted from gene expression. Here, we calculated bidirectional cross-association scores (predictivity and descriptivity) [...] Read more.
The availability of large-scale, collateral mRNA expression and RNAi data from diverse cancer cell types provides useful resources for the discovery of anticancer targets for which inhibitory efficacy can be predicted from gene expression. Here, we calculated bidirectional cross-association scores (predictivity and descriptivity) for each of approximately 18,000 genes identified from mRNA and RNAi (i.e., shRNA and sgRNA) data from colon cancer cell lines. The predictivity score measures the difference in RNAi efficacy between cell lines with high vs. low expression of the target gene, while the descriptivity score measures the differential mRNA expression between groups of cell lines exhibiting high vs. low RNAi efficacy. The mRNA expression of 90 and 74 genes showed significant (p < 0.01) cross-association scores with the shRNA and sgRNA data, respectively. The genes were found to be from diverse molecular classes and have different functions. Cross-association scores for the mRNA expression of six genes (CHAF1B, HNF1B, HTATSF1, IRS2, POLR2B and SATB2) with both shRNA and sgRNA efficacy were significant. These genes were interconnected in cancer-related transcriptional networks. Additional experimental validation confirmed that siHNF1B efficacy is correlated with HNF1B mRNA expression levels in diverse colon cancer cell lines. Furthermore, KIF26A and ZIC2 gene expression, with which shRNA efficacy displayed significant scores, were found to correlate with the survival rate from colon cancer patient data. This study demonstrates that bidirectional predictivity and descriptivity calculations between mRNA and RNAi data serve as useful resources for the discovery of predictive anticancer targets. Full article
►▼ Show Figures

Figure 1

21 pages, 10470 KiB  
Article
A Methylation-Based Reclassification of Bladder Cancer Based on Immune Cell Genes
by Qizhan Luo and Thomas-Alexander Vögeli
Cancers 2020, 12(10), 3054; https://doi.org/10.3390/cancers12103054 - 20 Oct 2020
Cited by 28 | Viewed by 4496
Abstract
Background: Bladder cancer is highly related to immune cell infiltration. This study aimed to develop a new classification of BC molecular subtypes based on immune-cell-associated CpG sites. Methods: The genes of 28 types of immune cells were obtained from previous studies. Then, methylation [...] Read more.
Background: Bladder cancer is highly related to immune cell infiltration. This study aimed to develop a new classification of BC molecular subtypes based on immune-cell-associated CpG sites. Methods: The genes of 28 types of immune cells were obtained from previous studies. Then, methylation sites corresponding to immune-cell-associated genes were acquired. Differentially methylated sites (DMSs) were identified between normal samples and bladder cancer samples. Unsupervised clustering analysis of differentially methylated sites was performed to divide the sites into several subtypes. Then, the potential mechanism of different subtypes was explored. Results: Bladder cancer patients were divided into three groups. The cluster 3 subtype had the best prognosis. Cluster 1 had the poorest prognosis. The distribution of immune cells, level of expression of checkpoints, stromal score, immune score, ESTIMATEScore, tumor purity, APC co_inhibition, APC co_stimulation, HLA, MHC class_I, Type I IFN Response, Type II IFN Response, and DNAss presented significant differences among the three subgroups. The distribution of genomic alterations was also different. Conclusions: The proposed classification was accurate and stable. BC patients could be divided into three subtypes based on the immune-cell-associated CpG sites. Specific biological signaling pathways, immune mechanisms, and genomic alterations were varied among the three subgroups. High-level immune infiltration was correlated with high-level methylation. The lower RNAss was associated with higher immune infiltration. The study of the intratumoral immune microenvironment may provide a new perspective for BC therapy. Full article
►▼ Show Figures

Figure 1

22 pages, 4024 KiB  
Article
Transcriptomics-Based Drug Repurposing Approach Identifies Novel Drugs against Sorafenib-Resistant Hepatocellular Carcinoma
by Kelly Regan-Fendt, Ding Li, Ryan Reyes, Lianbo Yu, Nissar A. Wani, Peng Hu, Samson T. Jacob, Kalpana Ghoshal, Philip R.O. Payne and Tasneem Motiwala
Cancers 2020, 12(10), 2730; https://doi.org/10.3390/cancers12102730 - 23 Sep 2020
Cited by 27 | Viewed by 4175
Abstract
Objective: Hepatocellular carcinoma (HCC) is frequently diagnosed in patients with late-stage disease who are ineligible for curative surgical therapies. The majority of patients become resistant to sorafenib, the only approved first-line therapy for advanced cancer, underscoring the need for newer, more effective drugs. [...] Read more.
Objective: Hepatocellular carcinoma (HCC) is frequently diagnosed in patients with late-stage disease who are ineligible for curative surgical therapies. The majority of patients become resistant to sorafenib, the only approved first-line therapy for advanced cancer, underscoring the need for newer, more effective drugs. The purpose of this study is to expedite identification of novel drugs against sorafenib resistant (SR)-HCC. Methods: We employed a transcriptomics-based drug repurposing method termed connectivity mapping using gene signatures from in vitro-derived SR Huh7 HCC cells. For proof of concept validation, we focused on drugs that were FDA-approved or under clinical investigation and prioritized two anti-neoplastic agents (dasatinib and fostamatinib) with targets associated with HCC. We also prospectively validated predicted gene expression changes in drug-treated SR Huh7 cells as well as identified and validated the targets of Fostamatinib in HCC. Results: Dasatinib specifically reduced the viability of SR-HCC cells that correlated with up-regulated activity of SRC family kinases, its targets, in our SR-HCC model. However, fostamatinib was able to inhibit both parental and SR HCC cells in vitro and in xenograft models. Ingenuity pathway analysis of fostamatinib gene expression signature from LINCS predicted JAK/STAT, PI3K/AKT, ERK/MAPK pathways as potential targets of fostamatinib that were validated by Western blot analysis. Fostamatinib treatment reversed the expression of genes that were deregulated in SR HCC. Conclusion: We provide proof of concept evidence for the validity of this drug repurposing approach for SR-HCC with implications for personalized medicine. Full article
►▼ Show Figures

Figure 1

25 pages, 5553 KiB  
Review
Applications of Genome-Wide Screening and Systems Biology Approaches in Drug Repositioning
by Elyas Mohammadi, Rui Benfeitas, Hasan Turkez, Jan Boren, Jens Nielsen, Mathias Uhlen and Adil Mardinoglu
Cancers 2020, 12(9), 2694; https://doi.org/10.3390/cancers12092694 - 21 Sep 2020
Cited by 15 | Viewed by 6757
Abstract
Modern drug discovery through de novo drug discovery entails high financial costs, low success rates, and lengthy trial periods. Drug repositioning presents a suitable approach for overcoming these issues by re-evaluating biological targets and modes of action of approved drugs. Coupling high-throughput technologies [...] Read more.
Modern drug discovery through de novo drug discovery entails high financial costs, low success rates, and lengthy trial periods. Drug repositioning presents a suitable approach for overcoming these issues by re-evaluating biological targets and modes of action of approved drugs. Coupling high-throughput technologies with genome-wide essentiality screens, network analysis, genome-scale metabolic modeling, and machine learning techniques enables the proposal of new drug–target signatures and uncovers unanticipated modes of action for available drugs. Here, we discuss the current issues associated with drug repositioning in light of curated high-throughput multi-omic databases, genome-wide screening technologies, and their application in systems biology/medicine approaches. Full article
►▼ Show Figures

Graphical abstract

22 pages, 5622 KiB  
Article
CeRNA Network Analysis Representing Characteristics of Different Tumor Environments Based on 1p/19q Codeletion in Oligodendrogliomas
by Ju Won Ahn, YoungJoon Park, Su Jung Kang, So Jung Hwang, Kyung Gi Cho, JaeJoon Lim and KyuBum Kwack
Cancers 2020, 12(9), 2543; https://doi.org/10.3390/cancers12092543 - 7 Sep 2020
Cited by 5 | Viewed by 4433 | Correction
Abstract
Oligodendroglioma (OD) is a subtype of glioma occurring in the central nervous system. The 1p/19q codeletion is a prognostic marker of OD with an isocitrate dehydrogenase (IDH) mutation and is associated with a clinically favorable overall survival (OS); however, the exact [...] Read more.
Oligodendroglioma (OD) is a subtype of glioma occurring in the central nervous system. The 1p/19q codeletion is a prognostic marker of OD with an isocitrate dehydrogenase (IDH) mutation and is associated with a clinically favorable overall survival (OS); however, the exact underlying mechanism remains unclear. Long non-coding RNAs (lncRNAs) have recently been suggested to regulate carcinogenesis and prognosis in cancer patients. Here, we performed in silico analyses using low-grade gliomas from datasets obtained from The Cancer Genome Atlas to investigate the effects of ceRNA with 1p/19q codeletion on ODs. Thus, we selected modules of differentially expressed genes that were closely related to 1p/19q codeletion traits using weighted gene co-expression network analysis and constructed 16 coding RNA–miRNA–lncRNA networks. The ceRNA network participated in ion channel activity, insulin secretion, and collagen network and extracellular matrix (ECM) changes. In conclusion, ceRNAs with a 1p/19q codeletion can create different tumor microenvironments via potassium ion channels and ECM composition changes; furthermore, differences in OS may occur. Moreover, if extrapolated to gliomas, our results can provide insights into the consequences of identical gene expression, indicating the possibility of tracking different biological processes in different subtypes of glioma. Full article
►▼ Show Figures

Figure 1

17 pages, 1464 KiB  
Article
Comprehensive Cohort Analysis of Mutational Spectrum in Early Onset Breast Cancer Patients
by Mohit K. Midha, Yu-Feng Huang, Hsiao-Hsiang Yang, Tan-Chi Fan, Nai-Chuan Chang, Tzu-Han Chen, Yu-Tai Wang, Wen-Hung Kuo, King-Jen Chang, Chen-Yang Shen, Alice L. Yu, Kuo-Ping Chiu and Chien-Jen Chen
Cancers 2020, 12(8), 2089; https://doi.org/10.3390/cancers12082089 - 28 Jul 2020
Cited by 10 | Viewed by 4224
Abstract
Early onset breast cancer (EOBC), diagnosed at age ~40 or younger, is associated with a poorer prognosis and higher mortality rate compared to breast cancer diagnosed at age 50 or older. EOBC poses a serious threat to public health and requires in-depth investigation. [...] Read more.
Early onset breast cancer (EOBC), diagnosed at age ~40 or younger, is associated with a poorer prognosis and higher mortality rate compared to breast cancer diagnosed at age 50 or older. EOBC poses a serious threat to public health and requires in-depth investigation. We studied a cohort comprising 90 Taiwanese female patients, aiming to unravel the underlying mechanisms of EOBC etiopathogenesis. Sequence data generated by whole-exome sequencing (WES) and whole-genome sequencing (WGS) from white blood cell (WBC)–tumor pairs were analyzed to identify somatic missense mutations, copy number variations (CNVs) and germline missense mutations. Similar to regular breast cancer, the key somatic mutation-susceptibility genes of EOBC include TP53 (40% prevalence), PIK3CA (37%), GATA3 (17%) and KMT2C (17%), which are frequently reported in breast cancer; however, the structural protein-coding genes MUC17 (19%), FLG (16%) and NEBL (11%) show a significantly higher prevalence in EOBC. Furthermore, the top 2 genes harboring EOBC germline mutations, MUC16 (19%) and KRT18 (19%), encode structural proteins. Compared to conventional breast cancer, an unexpectedly higher number of EOBC susceptibility genes encode structural proteins. We suspect that mutations in structural proteins may increase physical permeability to environmental hormones and carcinogens and cause breast cancer to occur at a young age. Full article
►▼ Show Figures

Figure 1

17 pages, 4901 KiB  
Article
Computational Identification of Gene Networks as a Biomarker of Neuroblastoma Risk
by Lidan Sun, Libo Jiang, Christa N. Grant, Hong-Gang Wang, Claudia Gragnoli, Zhenqiu Liu and Rongling Wu
Cancers 2020, 12(8), 2086; https://doi.org/10.3390/cancers12082086 - 28 Jul 2020
Cited by 11 | Viewed by 2926
Abstract
Neuroblastoma is a common cancer in children, affected by a number of genes that interact with each other through intricate but coordinated networks. Traditional approaches can only reconstruct a single regulatory network that is topologically not informative enough to explain the complexity of [...] Read more.
Neuroblastoma is a common cancer in children, affected by a number of genes that interact with each other through intricate but coordinated networks. Traditional approaches can only reconstruct a single regulatory network that is topologically not informative enough to explain the complexity of neuroblastoma risk. We implemented and modified an advanced model for recovering informative, omnidirectional, dynamic, and personalized networks (idopNetworks) from static gene expression data for neuroblastoma risk. We analyzed 3439 immune genes of neuroblastoma for 217 high-risk patients and 30 low-risk patients by which to reconstruct large patient-specific idopNetworks. By converting these networks into risk-specific representations, we found that the shift in patients from a low to high risk or from a high to low risk might be due to the reciprocal change of hub regulators. By altering the directions of regulation exerted by these hubs, it may be possible to reduce a high risk to a low risk. Results from a holistic, systems-oriented paradigm through idopNetworks can potentially enable oncologists to experimentally identify the biomarkers of neuroblastoma and other cancers. Full article
►▼ Show Figures

Figure 1

20 pages, 7662 KiB  
Article
A Multiplex Assay for the Stratification of Patients with Primary Central Nervous System Lymphoma Using Targeted Mass Spectrometry
by Daniel M. Waldera-Lupa, Gereon Poschmann, Nina Kirchgaessler, Omid Etemad-Parishanzadeh, Falk Baberg, Mareike Brocksieper, Sabine Seidel, Thomas Kowalski, Anna Brunn, Aiden Haghikia, Ralf Gold, Anja Stefanski, Martina Deckert, Uwe Schlegel and Kai Stühler
Cancers 2020, 12(7), 1732; https://doi.org/10.3390/cancers12071732 - 29 Jun 2020
Cited by 9 | Viewed by 3282
Abstract
Primary central nervous system lymphomas (PCNSL) account for approximately 2% to 3% of all primary brain tumors. Until now, neuropathological tumor tissue analysis, most frequently gained by stereotactic biopsy, is still the diagnostic gold standard. Here, we rigorously analyzed two independent patient cohorts [...] Read more.
Primary central nervous system lymphomas (PCNSL) account for approximately 2% to 3% of all primary brain tumors. Until now, neuropathological tumor tissue analysis, most frequently gained by stereotactic biopsy, is still the diagnostic gold standard. Here, we rigorously analyzed two independent patient cohorts comprising the clinical entities PCNSL (n = 47), secondary central nervous system lymphomas (SCNSL; n = 13), multiple sclerosis (MS, n = 23), glioma (n = 10), other tumors (n = 17) and tumor-free controls (n = 21) by proteomic approaches. In total, we identified more than 1220 proteins in the cerebrospinal fluid (CSF) and validated eight candidate biomarkers by a peptide-centric approach in an independent patient cohort (n = 63). Thus, we obtained excellent diagnostic accuracy for the stratification between PCNSL, MS and glioma patients as well as tumor-free controls for three peptides originating from the three proteins VSIG4, GPNMB4 and APOC2. The combination of all three biomarker candidates resulted in diagnostic accuracy with an area under the curve (AUC) of 0.901 (PCNSL vs. MS), AUC of 0.953 (PCNSL vs. glioma) and AUC 0.850 (PCNSL vs. tumor-free control). In summary, the determination of VSIG4, GPNMB4 and APOC2 in CSF as novel biomarkers for supporting the diagnosis of PCNSL is suggested. Full article
►▼ Show Figures

Figure 1

23 pages, 7854 KiB  
Article
TP53 Status, Patient Sex, and the Immune Response as Determinants of Lung Cancer Patient Survival
by Donald Freudenstein, Cassandra Litchfield, Franco Caramia, Gavin Wright, Benjamin J. Solomon, David Ball, Simon P. Keam, Paul Neeson, Ygal Haupt and Sue Haupt
Cancers 2020, 12(6), 1535; https://doi.org/10.3390/cancers12061535 - 11 Jun 2020
Cited by 26 | Viewed by 4862
Abstract
Lung cancer poses the greatest cancer-related death risk and males have poorer outcomes than females, for unknown reasons. Patient sex is not a biological variable considered in lung cancer standard of care. Correlating patient genetics with outcomes is predicted to open avenues for [...] Read more.
Lung cancer poses the greatest cancer-related death risk and males have poorer outcomes than females, for unknown reasons. Patient sex is not a biological variable considered in lung cancer standard of care. Correlating patient genetics with outcomes is predicted to open avenues for improved management. Using a bioinformatics approach across non-small cell lung cancer (NSCLC) subtypes, we identified where patient sex, mutation of the major tumor suppressor gene, Tumour protein P53 (TP53), and immune signatures stratified outcomes in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), among datasets of The Cancer Genome Atlas (TCGA). We exposed sex and TP53 gene mutations as prognostic for LUAD survival. Longest survival in LUAD occurred among females with wild-type (wt) TP53 genes, high levels of immune infiltration and enrichment for pathway signatures of Interferon Gamma (INF-γ), Tumour Necrosis Factor (TNF) and macrophages-monocytes. In contrast, poor survival in men with LUAD and wt TP53 genes corresponded with enrichment of Transforming Growth Factor Beta 1 (TGFB1, hereafter TGF-β) and wound healing signatures. In LUAD with wt TP53 genes, elevated gene expression of immune checkpoint CD274 (hereafter: PD-L1) and also protein 53 (p53) negative-regulators of the Mouse Double Minute (MDM)-family predict novel avenues for combined immunotherapies. LUSC is dominated by male smokers with TP53 gene mutations, while a minor population of TCGA LC patients with wt TP53 genes unexpectedly had the poorest survival, suggestive of a separate etiology. We conclude that advanced approaches to LUAD and LUSC therapy lie in the consideration of patient sex, TP53 gene mutation status and immune signatures. Full article
►▼ Show Figures

Figure 1

25 pages, 663 KiB  
Review
Radiomics Applications in Renal Tumor Assessment: A Comprehensive Review of the Literature
by Rodrigo Suarez-Ibarrola, Mario Basulto-Martinez, Alexander Heinze, Christian Gratzke and Arkadiusz Miernik
Cancers 2020, 12(6), 1387; https://doi.org/10.3390/cancers12061387 - 28 May 2020
Cited by 43 | Viewed by 4476
Abstract
Radiomics texture analysis offers objective image information that could otherwise not be obtained by radiologists′ subjective radiological interpretation. We investigated radiomics applications in renal tumor assessment and provide a comprehensive review. A detailed search of original articles was performed using the PubMed-MEDLINE database [...] Read more.
Radiomics texture analysis offers objective image information that could otherwise not be obtained by radiologists′ subjective radiological interpretation. We investigated radiomics applications in renal tumor assessment and provide a comprehensive review. A detailed search of original articles was performed using the PubMed-MEDLINE database until 20 March 2020 to identify English literature relevant to radiomics applications in renal tumor assessment. In total, 42 articles were included in the analysis and divided into four main categories: renal mass differentiation, nuclear grade prediction, gene expression-based molecular signatures, and patient outcome prediction. The main area of research involves accurately differentiating benign and malignant renal masses, specifically between renal cell carcinoma (RCC) subtypes and from angiomyolipoma without visible fat and oncocytoma. Nuclear grade prediction may enhance proper patient selection for risk-stratified treatment. Radiomics-predicted gene mutations may serve as surrogate biomarkers for high-risk disease, while predicting patients’ responses to targeted therapies and their outcomes will help develop personalized treatment algorithms. Studies generally reported the superiority of radiomics over expert radiological interpretation. Radiomics provides an alternative to subjective image interpretation for improving renal tumor diagnostic accuracy. Further incorporation of clinical and imaging data into radiomics algorithms will augment tumor prediction accuracy and enhance individualized medicine. Full article
►▼ Show Figures

Graphical abstract

15 pages, 3592 KiB  
Article
Pan-Cancer Analysis of Radiotherapy Benefits and Immune Infiltration in Multiple Human Cancers
by Pengbo Wen, Yang Gao, Bin Chen, Xiaojing Qi, Guanshuo Hu, An Xu, Junfeng Xia, Lijun Wu, Huayi Lu and Guoping Zhao
Cancers 2020, 12(4), 957; https://doi.org/10.3390/cancers12040957 - 13 Apr 2020
Cited by 12 | Viewed by 4899
Abstract
Response to radiotherapy (RT) in cancers varies widely among patients. Therefore, it is very important to predict who will benefit from RT before clinical treatment. Consideration of the immune tumor microenvironment (TME) could provide novel insight into tumor treatment options. In this study, [...] Read more.
Response to radiotherapy (RT) in cancers varies widely among patients. Therefore, it is very important to predict who will benefit from RT before clinical treatment. Consideration of the immune tumor microenvironment (TME) could provide novel insight into tumor treatment options. In this study, we investigated the link between immune infiltration status and clinical RT outcome in order to identify certain leukocyte subsets that could potentially influence the clinical RT benefit across cancers. By integrally analyzing the TCGA data across seven cancers, we identified complex associations between immune infiltration and patients RT outcomes. Besides, immune cells showed large differences in their populations in various cancers, and the most abundant cells were resting memory CD4 T cells. Additionally, the proportion of activated CD4 memory T cells and activated mast cells, albeit at low number, were closely related to RT overall survival in multiple cancers. Furthermore, a prognostic model for RT outcomes was established with good performance based on the immune infiltration status. Summarized, immune infiltration was found to be of significant clinical relevance to RT outcomes. These findings may help to shed light on the impact of tumor-associated immune cell infiltration on cancer RT outcomes, and identify biomarkers and therapeutic targets. Full article
►▼ Show Figures

Figure 1

26 pages, 5088 KiB  
Article
Utilizing Genome-Wide mRNA Profiling to Identify the Cytotoxic Chemotherapeutic Mechanism of Triazoloacridone C-1305 as Direct Microtubule Stabilization
by Jarosław Króliczewski, Sylwia Bartoszewska, Magdalena Dudkowska, Dorota Janiszewska, Agnieszka Biernatowska, David K. Crossman, Karol Krzymiński, Małgorzata Wysocka, Anna Romanowska, Maciej Baginski, Michal Markuszewski, Renata J. Ochocka, James F. Collawn, Aleksander F. Sikorski, Ewa Sikora and Rafal Bartoszewski
Cancers 2020, 12(4), 864; https://doi.org/10.3390/cancers12040864 - 2 Apr 2020
Cited by 7 | Viewed by 4043
Abstract
Rational drug design and in vitro pharmacology profiling constitute the gold standard in drug development pipelines. Problems arise, however, because this process is often difficult due to limited information regarding the complete identification of a molecule’s biological activities. The increasing affordability of genome-wide [...] Read more.
Rational drug design and in vitro pharmacology profiling constitute the gold standard in drug development pipelines. Problems arise, however, because this process is often difficult due to limited information regarding the complete identification of a molecule’s biological activities. The increasing affordability of genome-wide next-generation technologies now provides an excellent opportunity to understand a compound’s diverse effects on gene regulation. Here, we used an unbiased approach in lung and colon cancer cell lines to identify the early transcriptomic signatures of C-1305 cytotoxicity that highlight the novel pathways responsible for its biological activity. Our results demonstrate that C-1305 promotes direct microtubule stabilization as a part of its mechanism of action that leads to apoptosis. Furthermore, we show that C-1305 promotes G2 cell cycle arrest by modulating gene expression. The results indicate that C-1305 is the first microtubule stabilizing agent that also is a topoisomerase II inhibitor. This study provides a novel approach and methodology for delineating the antitumor mechanisms of other putative anticancer drug candidates. Full article
►▼ Show Figures

Figure 1

15 pages, 830 KiB  
Review
Artificial Intelligence and Digital Microscopy Applications in Diagnostic Hematopathology
by Hanadi El Achi and Joseph D. Khoury
Cancers 2020, 12(4), 797; https://doi.org/10.3390/cancers12040797 - 26 Mar 2020
Cited by 53 | Viewed by 7200
Abstract
Digital Pathology is the process of converting histology glass slides to digital images using sophisticated computerized technology to facilitate acquisition, evaluation, storage, and portability of histologic information. By its nature, digitization of analog histology data renders it amenable to analysis using deep learning/artificial [...] Read more.
Digital Pathology is the process of converting histology glass slides to digital images using sophisticated computerized technology to facilitate acquisition, evaluation, storage, and portability of histologic information. By its nature, digitization of analog histology data renders it amenable to analysis using deep learning/artificial intelligence (DL/AI) techniques. The application of DL/AI to digital pathology data holds promise, even if the scope of use cases and regulatory framework for deploying such applications in the clinical environment remains in the early stages. Recent studies using whole-slide images and DL/AI to detect histologic abnormalities in general and cancer in particular have shown encouraging results. In this review, we focus on these emerging technologies intended for use in diagnostic hematology and the evaluation of lymphoproliferative diseases. Full article
►▼ Show Figures

Figure 1

19 pages, 782 KiB  
Review
The Application of Deep Learning in Cancer Prognosis Prediction
by Wan Zhu, Longxiang Xie, Jianye Han and Xiangqian Guo
Cancers 2020, 12(3), 603; https://doi.org/10.3390/cancers12030603 - 5 Mar 2020
Cited by 238 | Viewed by 24846
Abstract
Deep learning has been applied to many areas in health care, including imaging diagnosis, digital pathology, prediction of hospital admission, drug design, classification of cancer and stromal cells, doctor assistance, etc. Cancer prognosis is to estimate the fate of cancer, probabilities of cancer [...] Read more.
Deep learning has been applied to many areas in health care, including imaging diagnosis, digital pathology, prediction of hospital admission, drug design, classification of cancer and stromal cells, doctor assistance, etc. Cancer prognosis is to estimate the fate of cancer, probabilities of cancer recurrence and progression, and to provide survival estimation to the patients. The accuracy of cancer prognosis prediction will greatly benefit clinical management of cancer patients. The improvement of biomedical translational research and the application of advanced statistical analysis and machine learning methods are the driving forces to improve cancer prognosis prediction. Recent years, there is a significant increase of computational power and rapid advancement in the technology of artificial intelligence, particularly in deep learning. In addition, the cost reduction in large scale next-generation sequencing, and the availability of such data through open source databases (e.g., TCGA and GEO databases) offer us opportunities to possibly build more powerful and accurate models to predict cancer prognosis more accurately. In this review, we reviewed the most recent published works that used deep learning to build models for cancer prognosis prediction. Deep learning has been suggested to be a more generic model, requires less data engineering, and achieves more accurate prediction when working with large amounts of data. The application of deep learning in cancer prognosis has been shown to be equivalent or better than current approaches, such as Cox-PH. With the burst of multi-omics data, including genomics data, transcriptomics data and clinical information in cancer studies, we believe that deep learning would potentially improve cancer prognosis. Full article
►▼ Show Figures

Figure 1

11 pages, 2655 KiB  
Article
The Crossroads of Precision Medicine and Therapeutic Decision-Making: Use of an Analytical Computational Platform to Predict Response to Cancer Treatments
by Amélie Boichard, Stephane B. Richard and Razelle Kurzrock
Cancers 2020, 12(1), 166; https://doi.org/10.3390/cancers12010166 - 9 Jan 2020
Cited by 6 | Viewed by 6517
Abstract
Metastatic cancer is a medical challenge that has been historically resistant to treatments. One area of leverage in cancer care is the development of molecularly-driven combination therapies, offering the possibility to overcome resistance. The selection of optimized treatments based on the complex molecular [...] Read more.
Metastatic cancer is a medical challenge that has been historically resistant to treatments. One area of leverage in cancer care is the development of molecularly-driven combination therapies, offering the possibility to overcome resistance. The selection of optimized treatments based on the complex molecular features of a patient’s tumor may be rendered easier by using a computer-assisted program. We used the PreciGENE® platform that uses multi-pathway molecular analysis to identify personalized therapeutic options. These options are ranked using a predictive score reflecting the degree to which a therapy or combination of therapies matches the patient’s biomarker profile. We searched PubMed from February 2010 to June 2017 for all patients described as exceptional responders who also had molecular data available. Altogether, 70 patients with cancer who had received 202 different treatment lines and who had responded (stable disease ≥12 months/partial or complete remission) to ≥1 regimen were curated. We demonstrate that an algorithm reflecting the degree to which patients were matched to the drugs administered correctly ranked the response to the regimens with a sensitivity of 84% and a specificity of 77%. The difference in matching score between successful and unsuccessful treatment lines was significant (median, 65% versus 0%, p-value <0.0001). Full article
►▼ Show Figures

Figure 1

2019

Jump to: 2024, 2023, 2022, 2021, 2020

14 pages, 1436 KiB  
Article
Parallel Structure Deep Neural Network Using CNN and RNN with an Attention Mechanism for Breast Cancer Histology Image Classification
by Hongdou Yao, Xuejie Zhang, Xiaobing Zhou and Shengyan Liu
Cancers 2019, 11(12), 1901; https://doi.org/10.3390/cancers11121901 - 29 Nov 2019
Cited by 101 | Viewed by 8258
Abstract
In this paper, we present a new deep learning model to classify hematoxylin–eosin-stained breast biopsy images into four classes (normal tissues, benign lesions, in situ carcinomas, and invasive carcinomas). Our model uses a parallel structure consist of a convolutional neural network (CNN) and [...] Read more.
In this paper, we present a new deep learning model to classify hematoxylin–eosin-stained breast biopsy images into four classes (normal tissues, benign lesions, in situ carcinomas, and invasive carcinomas). Our model uses a parallel structure consist of a convolutional neural network (CNN) and a recurrent neural network (RNN) for image feature extraction, which is greatly different from the common existed serial method of extracting image features by CNN and then inputting them into RNN. Then, we introduce a special perceptron attention mechanism, which is derived from the natural language processing (NLP) field, to unify the features extracted by the two different neural network structures of the model. In the convolution layer, general batch normalization is replaced by the new switchable normalization method. And the latest regularization technology, targeted dropout, is used to substitute for the general dropout in the last three fully connected layers of the model. In the testing phase, we use the model fusion method and test time augmentation technology on three different datasets of hematoxylin–eosin-stained breast biopsy images. The results demonstrate that our model significantly outperforms state-of-the-art methods. Full article
►▼ Show Figures

Figure 1

14 pages, 2704 KiB  
Article
Delineation of Tumor Migration Paths by Using a Bayesian Biogeographic Approach
by Antonia Chroni, Tracy Vu, Sayaka Miura and Sudhir Kumar
Cancers 2019, 11(12), 1880; https://doi.org/10.3390/cancers11121880 - 27 Nov 2019
Cited by 10 | Viewed by 3967
Abstract
Understanding tumor progression and metastatic potential are important in cancer biology. Metastasis is the migration and colonization of clones in secondary tissues. Here, we posit that clone migration events between tumors resemble the dispersal of individuals between distinct geographic regions. This similarity makes [...] Read more.
Understanding tumor progression and metastatic potential are important in cancer biology. Metastasis is the migration and colonization of clones in secondary tissues. Here, we posit that clone migration events between tumors resemble the dispersal of individuals between distinct geographic regions. This similarity makes Bayesian biogeographic analysis suitable for inferring cancer cell migration paths. We evaluated the accuracy of a Bayesian biogeography method (BBM) in inferring metastatic patterns and compared it with the accuracy of a parsimony-based approach (metastatic and clonal history integrative analysis, MACHINA) that has been specifically developed to infer clone migration patterns among tumors. We used computer-simulated datasets in which simple to complex migration patterns were modeled. BBM and MACHINA were effective in reliably reconstructing simple migration patterns from primary tumors to metastases. However, both of them exhibited a limited ability to accurately infer complex migration paths that involve the migration of clones from one metastatic tumor to another and from metastasis to the primary tumor. Therefore, advanced computational methods are still needed for the biologically realistic tracing of migration paths and to assess the relative preponderance of different types of seeding and reseeding events during cancer progression in patients. Full article
►▼ Show Figures

Graphical abstract

14 pages, 1792 KiB  
Article
Targeted-Gene Sequencing to Catch Triple Negative Breast Cancer Heterogeneity before and after Neoadjuvant Chemotherapy
by Serena Di Cosimo, Valentina Appierto, Marco Silvestri, Giancarlo Pruneri, Andrea Vingiani, Federica Perrone, Adele Busico, Secondo Folli, Gianfranco Scaperrotta, Filippo Guglielmo de Braud, Giulia Valeria Bianchi, Stefano Cavalieri, Maria Grazia Daidone and Matteo Dugo
Cancers 2019, 11(11), 1753; https://doi.org/10.3390/cancers11111753 - 8 Nov 2019
Cited by 15 | Viewed by 4481
Abstract
Triple negative breast cancer (TNBC) patients not attaining pathological Complete Response (pCR) after neo-adjuvant chemotherapy (NAC) have poor prognosis. We characterized 19 patients for somatic mutations in primary tumor biopsy and residual disease (RD) at surgery by 409 cancer-related gene sequencing (IonAmpliSeqTM Comprehensive [...] Read more.
Triple negative breast cancer (TNBC) patients not attaining pathological Complete Response (pCR) after neo-adjuvant chemotherapy (NAC) have poor prognosis. We characterized 19 patients for somatic mutations in primary tumor biopsy and residual disease (RD) at surgery by 409 cancer-related gene sequencing (IonAmpliSeqTM Comprehensive Cancer Panel). A median of four (range 1–66) genes was mutated in each primary tumor biopsy, and the most common mutated gene was TP53 followed by a long tail of low frequency mutations. There were no recurrent mutations significantly associated with pCR. However, half of patients with RD had primary tumor biopsy with mutations in genes related to the immune system compared with none of those achieving pCR. Overall, the number of mutations showed a downward trend in post- as compared to pre-NAC samples. PIK3CA was the most common altered gene after NAC. The mutational profile of TNBC during treatment as inferred from patterns of mutant allele frequencies in matched pre-and post-NAC samples showed that RD harbored alterations of cell cycle progression, PI3K/Akt/mTOR, and EGFR tyrosine kinase inhibitor-resistance pathways. Our findings support the use of targeted-gene sequencing for TNBC therapeutic development, as patients without pCR may present mutations of immune-related pathways in their primary tumor biopsy, or actionable targets in the RD. Full article
►▼ Show Figures

Figure 1

15 pages, 2739 KiB  
Article
Coupled Genome-Wide DNA Methylation and Transcription Analysis Identified Rich Biomarkers and Drug Targets in Triple-Negative Breast Cancer
by Maoni Guo, Siddharth Sinha and San Ming Wang
Cancers 2019, 11(11), 1724; https://doi.org/10.3390/cancers11111724 - 4 Nov 2019
Cited by 10 | Viewed by 4270
Abstract
Triple-negative breast cancer (TNBC) has poor clinical prognosis. Lack of TNBC-specific biomarkers prevents active clinical intervention. We reasoned that TNBC must have its specific signature due to the lack of three key receptors to distinguish TNBC from other types of breast cancer. We [...] Read more.
Triple-negative breast cancer (TNBC) has poor clinical prognosis. Lack of TNBC-specific biomarkers prevents active clinical intervention. We reasoned that TNBC must have its specific signature due to the lack of three key receptors to distinguish TNBC from other types of breast cancer. We also reasoned that coupling methylation and gene expression as a single unit may increase the specificity for the detected TNBC signatures. We further reasoned that choosing the proper controls may be critical to increasing the sensitivity to identify TNBC-specific signatures. Furthermore, we also considered that specific drugs could target the detected TNBC-specific signatures. We developed a system to identify potential TNBC signatures. It consisted of (1) coupling methylation and expression changes in TNBC to identify the methylation-regulated signature genes for TNBC; (2) using TPBC (triple-positive breast cancer) as the control to detect TNBC-specific signature genes; (3) searching in the drug database to identify those targeting TNBC signature genes. Using this system, we identified 114 genes with both altered methylation and expression, and 356 existing drugs targeting 10 of the 114 genes. Through docking and molecular dynamics simulation, we determined the structural basis between sapropterin, a drug used in the treatment of tetrahydrobiopterin deficiency, and PTGS2, a TNBC signature gene involved in the conversion of arachidonic acid to prostaglandins. Our study reveals the existence of rich TNBC-specific signatures, and many can be drug target and biomarker candidates for clinical applications. Full article
►▼ Show Figures

Figure 1

17 pages, 4084 KiB  
Article
Construction and Validation of an Immune-Related Prognostic Model Based on TP53 Status in Colorectal Cancer
by Xiaojuan Zhao, Jianzhong Liu, Shuzhen Liu, Fangfang Yang and Erfei Chen
Cancers 2019, 11(11), 1722; https://doi.org/10.3390/cancers11111722 - 4 Nov 2019
Cited by 20 | Viewed by 4919
Abstract
Growing evidence has indicated that prognostic biomarkers have a pivotal role in tumor and immunity biological processes. TP53 mutation can cause a range of changes in immune response, progression, and prognosis of colorectal cancer (CRC). Thus, we aim to build an immunoscore prognostic [...] Read more.
Growing evidence has indicated that prognostic biomarkers have a pivotal role in tumor and immunity biological processes. TP53 mutation can cause a range of changes in immune response, progression, and prognosis of colorectal cancer (CRC). Thus, we aim to build an immunoscore prognostic model that may enhance the prognosis of CRC from an immunological perspective. We estimated the proportion of immune cells in the GSE39582 public dataset using the CIBERSORT (Cell type identification by estimating relative subset of known RNA transcripts) algorithm. Prognostic genes that were used to establish the immunoscore model were generated by the LASSO (Least absolute shrinkage and selection operator) Cox regression model. We established and validated the immunoscore model in GEO (Gene Expression Omnibus) and TCGA (The Cancer Genome Atlas) cohorts, respectively; significant differences of overall survival analysis were found between the low and high immunoscore groups or TP53 subgroups. In the multivariable Cox analysis, we observed that the immunoscore was an independent prognostic factor both in the GEO cohort (HR (Hazard ratio) 1.76, 95% CI (confidence intervals): 1.26–2.46) and the TCGA cohort (HR 1.95, 95% CI: 1.20–3.18). Furthermore, we established a nomogram for clinical application, and the results suggest that the nomogram is a better predictive model for prognosis than immunoscore or TNM staging. Full article
►▼ Show Figures

Figure 1

14 pages, 4098 KiB  
Article
Mutational Landscape of the BAP1 Locus Reveals an Intrinsic Control to Regulate the miRNA Network and the Binding of Protein Complexes in Uveal Melanoma
by Amit Sharma, Arijit Biswas, Hongde Liu, Sagnik Sen, Anoosha Paruchuri, Panagiotis Katsonis, Olivier Lichtarge, Tikam Chand Dakal, Ujjwal Maulik, M. Michael Gromiha, Sanghamitra Bandyopadhyay, Michael Ludwig, Frank G. Holz, Karin U. Loeffler and Martina C. Herwig-Carl
Cancers 2019, 11(10), 1600; https://doi.org/10.3390/cancers11101600 - 19 Oct 2019
Cited by 30 | Viewed by 7092
Abstract
The BAP1 (BRCA1-associated protein 1) gene is associated with a variety of human cancers. With its gene product being a nuclear ubiquitin carboxy-terminal hydrolase with deubiquitinase activity, BAP1 acts as a tumor suppressor gene with potential pleiotropic effects in multiple tumor types. Herein, [...] Read more.
The BAP1 (BRCA1-associated protein 1) gene is associated with a variety of human cancers. With its gene product being a nuclear ubiquitin carboxy-terminal hydrolase with deubiquitinase activity, BAP1 acts as a tumor suppressor gene with potential pleiotropic effects in multiple tumor types. Herein, we focused specifically on uveal melanoma (UM) in which BAP1 mutations are associated with a metastasizing phenotype and decreased survival rates. We identified the ubiquitin carboxyl hydrolase (UCH) domain as a major hotspot region for the pathogenic mutations with a high evolutionary action (EA) score. This also includes the mutations at conserved catalytic sites and the ones overlapping with the phosphorylation residues. Computational protein interaction studies revealed that distant BAP1-associated protein complexes (FOXK2, ASXL1, BARD1, BRCA1) could be directly impacted by this mutation paradigm. We also described the conformational transition related to BAP1-BRCA-BARD1 complex, which may pose critical implications for mutations, especially at the docking interfaces of these three proteins. The mutations affect - independent of being somatic or germline - the binding affinity of miRNAs embedded within the BAP1 locus, thereby altering the unique regulatory network. Apart from UM, BAP1 gene expression and survival associations were found to be predictive for the prognosis in several (n = 29) other cancer types. Herein, we suggest that although BAP1 is conceptually a driver gene in UM, it might contribute through its interaction partners and its regulatory miRNA network to various aspects of cancer. Taken together, these findings will pave the way to evaluate BAP1 in a variety of other human cancers with a shared mutational spectrum. Full article
►▼ Show Figures

Graphical abstract

16 pages, 2769 KiB  
Article
Next-Generation Sequencing Improves Diagnosis, Prognosis and Clinical Management of Myeloid Neoplasms
by Diego Carbonell, Julia Suárez-González, María Chicano, Cristina Andrés-Zayas, Juan Carlos Triviño, Gabriela Rodríguez-Macías, Mariana Bastos-Oreiro, Patricia Font, Mónica Ballesteros, Paula Muñiz, Pascual Balsalobre, Mi Kwon, Javier Anguita, José Luis Díez-Martín, Ismael Buño and Carolina Martínez-Laperche
Cancers 2019, 11(9), 1364; https://doi.org/10.3390/cancers11091364 - 13 Sep 2019
Cited by 26 | Viewed by 5038
Abstract
Molecular diagnosis of myeloid neoplasms (MN) is based on the detection of multiple genetic alterations using various techniques. Next-generation sequencing (NGS) has been proved as a useful method for analyzing many genes simultaneously. In this context, we analyzed diagnostic samples from 121 patients [...] Read more.
Molecular diagnosis of myeloid neoplasms (MN) is based on the detection of multiple genetic alterations using various techniques. Next-generation sequencing (NGS) has been proved as a useful method for analyzing many genes simultaneously. In this context, we analyzed diagnostic samples from 121 patients affected by MN and ten relapse samples from a subset of acute myeloid leukemia patients using two enrichment-capture NGS gene panels. Pathogenicity classification of variants was enhanced by the development and application of a custom onco-hematology score. A total of 278 pathogenic variants were detected in 84% of patients. For structural alterations, 82% of those identified by cytogenetics were detected by NGS, 25 of 31 copy number variants and three out of three translocations. The detection of variants using NGS changed the diagnosis of seven patients and the prognosis of 15 patients and enabled us to identify 44 suitable candidates for clinical trials. Regarding AML, six of the ten relapsed patients lost or gained variants, comparing with diagnostic samples. In conclusion, the use of NGS panels in MN improves genetic characterization of the disease compared with conventional methods, thus demonstrating its potential clinical utility in routine clinical testing. This approach leads to better-adjusted treatments for each patient. Full article
►▼ Show Figures

Figure 1

16 pages, 1822 KiB  
Article
In Silico Drug Prescription for Targeting Cancer Patient Heterogeneity and Prediction of Clinical Outcome
by Elena Piñeiro-Yáñez, María José Jiménez-Santos, Gonzalo Gómez-López and Fátima Al-Shahrour
Cancers 2019, 11(9), 1361; https://doi.org/10.3390/cancers11091361 - 13 Sep 2019
Cited by 4 | Viewed by 3936
Abstract
In silico drug prescription tools for precision cancer medicine can match molecular alterations with tailored candidate treatments. These methodologies require large and well-annotated datasets to systematically evaluate their performance, but this is currently constrained by the lack of complete patient clinicopathological data. Moreover, [...] Read more.
In silico drug prescription tools for precision cancer medicine can match molecular alterations with tailored candidate treatments. These methodologies require large and well-annotated datasets to systematically evaluate their performance, but this is currently constrained by the lack of complete patient clinicopathological data. Moreover, in silico drug prescription performance could be improved by integrating additional tumour information layers like intra-tumour heterogeneity (ITH) which has been related to drug response and tumour progression. PanDrugs is an in silico drug prescription method which prioritizes anticancer drugs combining both biological and clinical evidence. We have systematically evaluated PanDrugs in the Genomic Data Commons repository (GDC). Our results showed that PanDrugs is able to establish an a priori stratification of cancer patients treated with Epidermal Growth Factor Receptor (EGFR) inhibitors. Patients labelled as responders according to PanDrugs predictions showed a significantly increased overall survival (OS) compared to non-responders. PanDrugs was also able to suggest alternative tailored treatments for non-responder patients. Additionally, PanDrugs usefulness was assessed considering spatial and temporal ITH in cancer patients and showed that ITH can be approached therapeutically proposing drugs or combinations potentially capable of targeting the clonal diversity. In summary, this study is a proof of concept where PanDrugs predictions have been correlated to OS and can be useful to manage ITH in patients while increasing therapeutic options and demonstrating its clinical utility. Full article
►▼ Show Figures

Figure 1

Back to TopTop