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Feature Papers in Section "Cancer Biomarkers" in 2023–2024
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Feature Papers in Section "Cancer Biomarkers" in 2023–2024

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Biomarkers".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 10694

Special Issue Editor

Prof. Dr. Maxim V. Berezovski

E-Mail Website
Guest Editor
Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, ON K1N 6N5, Canada
Interests: glioblastoma; lung cancer; molecular diagnostics; circulating tumor cells; tumor-derived exosomes; aptamers; proteomics; biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Despite significant advances in the understanding and treatment of cancers, early detection and personalized therapeutic strategies remain essential in improving patients’ outcomes. Cancer biomarkers are crucial tools in this endeavor, providing insights that guide both research and clinical practice. Recognizing the critical role that biomarkers play, we are pleased to present this Special Issue dedicated exclusively to the latest research and advancements in cancer biomarkers.

The topics of interest include, but are not limited to:

Biomarkers Discovery: Exploring new molecular, genetic, and proteomic markers, which could serve as indicators of cancer initiation, progression, or responses to therapy.

Biomarker Validation and Clinical Implementation: Addressing the challenges and methodologies associated with translating laboratory findings into clinically applicable tools.

Precision Medicine and Targeted Therapies: Examining how cancer biomarkers are driving individualized treatment plans that cater to the unique characteristics of each patient's cancer.

Innovations in Detection and Analysis: Surveying the technological advancements that are enabling more precise, reliable, and cost-effective biomarker evaluation.

This Special Issue brings together a diverse array of contributions from prominent researchers, clinicians, and experts in oncology, genetics, biochemistry, and other interdisciplinary fields. The collaborative nature of these works illuminates the multifaceted approach required to realize the full potential of cancer biomarkers. Original articles, systematic reviews, and review papers are all welcomed. The aim is to have a collection of at least 10 articles, which we would assist you with, and the Special Issue may printed in book form if this goal is achieved.

We look forward to receiving your contributions.

Prof. Dr. Maxim V. Berezovski
Guest 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 special issue 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.

Keywords

  • RNA and miRNA biomarkers
  • DNA biomarkers
  • cell-free DNA
  • protein biomarkers
  • metabolomic biomarkers
  • mutational biomarkers
  • circulating tumor cell (CTC) biomarkers
  • tumor-derived extracellular vesicle (tEV) biomarkers
  • cellular biomarkers
  • imaging biomarkers
  • clinical biomarkers
  • biomarkers of drug response
  • biomarkers of genetic predisposition to cancer
  • epigenetic biomarkers
  • biomarkers of cancer outcomes

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Related Special Issue

Published Papers (11 papers)

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17 pages, 3139 KiB  
Article
Discovery, Validation and Mechanistic Study of XPO1 Inhibition in the Treatment of Triple-Negative Breast Cancer
by Amy L. Paulson, Robert F. Gruener, Adam M. Lee and R. Stephanie Huang
Cancers 2024, 16(23), 3980; https://doi.org/10.3390/cancers16233980 - 27 Nov 2024
Viewed by 360
Abstract
Background/Objectives: Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer with limited treatment options. The nuclear export protein XPO1 has emerged as a potential therapeutic target in cancer, but its role in TNBC has not been fully characterized. This study [...] Read more.
Background/Objectives: Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer with limited treatment options. The nuclear export protein XPO1 has emerged as a potential therapeutic target in cancer, but its role in TNBC has not been fully characterized. This study investigates the potential of repurposing selinexor, an FDA-approved XPO1 inhibitor, as a novel therapeutic options for TNBC. Methods: A computational drug repurposing pipeline was used to predict patient tumor responses to hundreds of drugs. We identified XPO1 inhibitors as a candidate drug and validated its efficacy on an independent patient dataset and across various TNBC cell lines. RNA-sequencing after longitudinal XPO1 inhibition and further mechanistic studies were performed to explore and confirm the leading causes of TNBC cell sensitivity to XPO1 inhibition. Results: Selinexor significantly reduce the viability of a variety of TNBC cell lines. Mechanistically, selinexor induces TNBC cell death by inhibiting the NF-kB pathway through nuclear retention of NFKBIA. This effect was consistent across multiple TNBC cell lines. Conclusions: XPO1 inhibitors show promise as targeted therapies for TNBC patients. New mechanistic insight into the causes leading to TNBC sensitivity to XPO1-inhibition-mediated cell death warrant further clinical trials to evaluate the safety and efficacy in TNBC. Full article
(This article belongs to the Special Issue Feature Papers in Section "Cancer Biomarkers" in 2023–2024)
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13 pages, 2077 KiB  
Article
Prognostic Role of Inflammatory and Nutritional Biomarkers in Non-Small-Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors Alone or in Combination with Chemotherapy as First-Line
by Antonello Veccia, Mariachiara Dipasquale, Stefania Kinspergher and Orazio Caffo
Cancers 2024, 16(22), 3871; https://doi.org/10.3390/cancers16223871 - 19 Nov 2024
Viewed by 405
Abstract
Introduction: In recent years, several inflammation-related factors and nutritional parameters have been evaluated to develop prognostic scores as potential biomarkers in non-small-cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs). The aim of this study was to retrospectively investigate the prognostic role [...] Read more.
Introduction: In recent years, several inflammation-related factors and nutritional parameters have been evaluated to develop prognostic scores as potential biomarkers in non-small-cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs). The aim of this study was to retrospectively investigate the prognostic role of the advanced lung cancer inflammation (ALI) index, lung immune prognostic index (LIPI), prognostic nutritional index (PNI) and systemic inflammation score (SIS) in metastatic NSCLC patients receiving ICI alone or in combination with chemotherapy. Methods and patients: We retrospectively included 191 patients with advanced NSCLC who received first-line ICI with or without chemotherapy from 2017 to 2024. The association between pretreatment ALI, LIPI, PNI, and SIS and overall survival (OS) was evaluated using the Kaplan–Meier method and Cox regression models. Results: After a median follow-up of 27.7 months, significantly longer OS was associated with an ALI score > 18 vs. ≤18 (18.0 vs. 7.3 months; p = 0.00111), LIPI score 0 vs. 1 and 2 [18.9 vs. 8.2 and 4.2 months; (p = 0.001)], PNI ≥ 45 vs. <45 (22.7 vs. 9.6 months; p = 0.002), and SIS score 0 vs. 1 and 2 (27.4 vs. 7.1 and 8.6 months, respectively; p < 0.001). The OS benefit was independent of treatment (ICI vs. ICI + chemotherapy). At multivariate analysis, pretreatment albumin was positively associated with OS, while ECOG PS 1 and liver metastases were negatively associated with OS. Conclusions: Inflammatory and nutritional biomarkers such as the ALI, LIPI, PNI, and SIS represent useful tools to prognosticate survival in metastatic lung cancer patients treated with ICI alone or in combination with chemotherapy as first-line. Full article
(This article belongs to the Special Issue Feature Papers in Section "Cancer Biomarkers" in 2023–2024)
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10 pages, 536 KiB  
Article
Validation of the Scottish Inflammatory Prognostic Score (SIPS) in NSCLC Patients Treated with First-Line Pembrolizumab
by Igor Gomez-Randulfe, Fabio Gomes, Melanie MacKean, Iain Phillips and Mark Stares
Cancers 2024, 16(22), 3833; https://doi.org/10.3390/cancers16223833 - 14 Nov 2024
Viewed by 493
Abstract
Background: The Scottish Inflammatory Prognostic Score (SIPS), combining albumin (≥/<35 g/L) and neutrophil count (≤/>7.5 × 109/L), has been identified as a prognostic biomarker for patients with non-small cell lung cancer (NSCLC) undergoing treatment with pembrolizumab monotherapy. We sought to validate [...] Read more.
Background: The Scottish Inflammatory Prognostic Score (SIPS), combining albumin (≥/<35 g/L) and neutrophil count (≤/>7.5 × 109/L), has been identified as a prognostic biomarker for patients with non-small cell lung cancer (NSCLC) undergoing treatment with pembrolizumab monotherapy. We sought to validate this biomarker of systemic inflammation in an external cohort. Methods: Patients treated with first-line pembrolizumab for advanced NSCLC with programmed death-ligand 1 (PD-L1) expression ≥ 50% at an English cancer centre were identified. Pre-treatment clinicopathological characteristics and the SIPS were recorded. The relationship between these and progression-free survival (PFS) and overall survival (OS) was examined. Results: Among 257 patients evaluated, 56% (n = 144) were classified as SIPS 0, 36% (n = 93) as SIPS 1, and 8% (n = 20) as SIPS 2. Factors such as age, performance status (PS) and brain metastases presence were significantly correlated with SIPS categories. Multivariate analysis revealed that both SIPS and PD-L1 status were independently associated with PFS and OS. The combination of SIPS with either PS or PD-L1 expression enhanced the ability to detect patients with the most favourable or poorest survival. Conclusions: Our study confirms the prognostic significance of the SIPS in patients with advanced NSCLC treated with pembrolizumab in the context of high PD-L1 expression. SIPS offers a straightforward, clinically applicable approach to patient stratification, potentially guiding therapeutic decisions and enhancing outcomes in advanced NSCLC. Future research should focus on validating these findings in prospective studies and exploring the integration of SIPS into clinical practice, alongside other prognostic markers, to optimize treatment strategies. Full article
(This article belongs to the Special Issue Feature Papers in Section "Cancer Biomarkers" in 2023–2024)
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17 pages, 2334 KiB  
Article
Prospective Screening of Cancer Syndromes in Patients with Mesenchymal Tumors
by Ingegerd Öfverholm, Yingbo Lin, Julia Mondini, John Hardingz, Robert Bränström, Panagiotis Tsagkozis, Valtteri Wirta, Anna Gellerbring, Johan Lindberg, Venkatesh Chellappa, Markus Mayrhofer, Cecilia Haglund, Felix Haglund de Flon and Karin Wallander
Cancers 2024, 16(22), 3816; https://doi.org/10.3390/cancers16223816 - 13 Nov 2024
Viewed by 603
Abstract
Background: The etiology of most mesenchymal tumors is unknown, and knowledge about syndromes with an increased risk of tumors in bone or soft tissue is sparse. Methods: We present a prospective germline analysis of 312 patients with tumors suspected of being sarcomas at [...] Read more.
Background: The etiology of most mesenchymal tumors is unknown, and knowledge about syndromes with an increased risk of tumors in bone or soft tissue is sparse. Methods: We present a prospective germline analysis of 312 patients with tumors suspected of being sarcomas at a tertiary sarcoma center. Germline and tumor whole genome sequencing, tumor transcriptome, and methylome analyses were performed. Results: Germline pathogenic or likely pathogenic variants associated with an increased risk of tumors were detected in 24 patients (8%), of which 11 (4%) harbored a detectable second hit in the tumor. Second hits were confirmed in genes with (NF1, RB1, TP53, EXT2, and SDHC) and without (ATM, CDC73, MLH1, MSH6, POLG, and KCNQ1) known association with mesenchymal tumor predisposition. Sarcomas from two Lynch syndrome patients showed mismatch repair deficiency, predicting a treatment response to immune checkpoint inhibitors (Level 1 biomarker according to the FDA (Federal Drug Administration) and ESMO (European Society for Medical Oncology)). None of the three CHEK2 carriers had a second hit in the tumor, suggesting a weak link to sarcoma. Conclusions: We conclude that second-hit analyses can be used in standard of care to identify syndrome-related tumors. This approach can help distinguish true manifestations of tumor syndromes from unrelated germline findings and enhance the understanding of germline predisposition in soft tissue tumors. Prospective screening using germline whole genome sequencing should be considered when comprehensive somatic sequencing is introduced into clinical practice. Full article
(This article belongs to the Special Issue Feature Papers in Section "Cancer Biomarkers" in 2023–2024)
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21 pages, 28562 KiB  
Article
Deep-Learning-Based Approach in Cancer-Region Assessment from HER2-SISH Breast Histopathology Whole Slide Images
by Zaka Ur Rehman, Mohammad Faizal Ahmad Fauzi, Wan Siti Halimatul Munirah Wan Ahmad, Fazly Salleh Abas, Phaik-Leng Cheah, Seow-Fan Chiew and Lai-Meng Looi
Cancers 2024, 16(22), 3794; https://doi.org/10.3390/cancers16223794 - 11 Nov 2024
Viewed by 636
Abstract
Fluorescence in situ hybridization (FISH) is widely regarded as the gold standard for evaluating human epidermal growth factor receptor 2 (HER2) status in breast cancer; however, it poses challenges such as the need for specialized training and issues related to signal degradation from [...] Read more.
Fluorescence in situ hybridization (FISH) is widely regarded as the gold standard for evaluating human epidermal growth factor receptor 2 (HER2) status in breast cancer; however, it poses challenges such as the need for specialized training and issues related to signal degradation from dye quenching. Silver-enhanced in situ hybridization (SISH) serves as an automated alternative, employing permanent staining suitable for bright-field microscopy. Determining HER2 status involves distinguishing between “Amplified” and “Non-Amplified” regions by assessing HER2 and centromere 17 (CEN17) signals in SISH-stained slides. This study is the first to leverage deep learning for classifying Normal, Amplified, and Non-Amplified regions within HER2-SISH whole slide images (WSIs), which are notably more complex to analyze compared to hematoxylin and eosin (H&E)-stained slides. Our proposed approach consists of a two-stage process: first, we evaluate deep-learning models on annotated image regions, and then we apply the most effective model to WSIs for regional identification and localization. Subsequently, pseudo-color maps representing each class are overlaid, and the WSIs are reconstructed with these mapped regions. Using a private dataset of HER2-SISH breast cancer slides digitized at 40× magnification, we achieved a patch-level classification accuracy of 99.9% and a generalization accuracy of 78.8% by applying transfer learning with a Vision Transformer (ViT) model. The robustness of the model was further evaluated through k-fold cross-validation, yielding an average performance accuracy of 98%, with metrics reported alongside 95% confidence intervals to ensure statistical reliability. This method shows significant promise for clinical applications, particularly in assessing HER2 expression status in HER2-SISH histopathology images. It provides an automated solution that can aid pathologists in efficiently identifying HER2-amplified regions, thus enhancing diagnostic outcomes for breast cancer treatment. Full article
(This article belongs to the Special Issue Feature Papers in Section "Cancer Biomarkers" in 2023–2024)
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12 pages, 3079 KiB  
Article
miR-3065-5p and miR-26a-5p as Clinical Biomarkers in Colorectal Cancer: A Translational Study
by Berenice Carbajal-López, Antonio Daniel Martínez-Gutierrez, Eduardo O. Madrigal-Santillán, Germán Calderillo-Ruiz, José Antonio Morales-González, Jossimar Coronel-Hernández, Joey Lockhart, Oliver Millan-Catalan, Monica G. Mendoza-Rodriguez, Leonardo S. Lino-Silva, Germán Calderillo-Trejo, Ronen Sumagin, Carlos Pérez-Plasencia and Eloy Andrés Pérez-Yépez
Cancers 2024, 16(21), 3649; https://doi.org/10.3390/cancers16213649 - 29 Oct 2024
Viewed by 601
Abstract
Background/Objectives: The prognosis of colorectal cancer (CRC) is mainly based on the clinical stage; however, CRC is considered a complex disease due to its molecular heterogeneity. The development of novel biomarkers to improve patients’ diagnosis and prognosis remains fundamental. Methods: A [...] Read more.
Background/Objectives: The prognosis of colorectal cancer (CRC) is mainly based on the clinical stage; however, CRC is considered a complex disease due to its molecular heterogeneity. The development of novel biomarkers to improve patients’ diagnosis and prognosis remains fundamental. Methods: A cohort of forty-nine CRC patients from the National Cancer Institute of Mexico was included to collect clinical and miRNA expression data. The expression of a group of miRNAs was compared between CRC and non-tumoral adjacent tissues. Prognosis assessment considering each miRNA expression was tested using Kaplan–Meier survival curves and Cox regressions. Statistical significance was defined as p ≤ 0.05. Trial registration: Retrospective study No.2021/046. Results: miR-3065-5p and miR-26a-5p expression differed between non-tumoral adjacent and tumoral tissues (p = 0.02). In terms of overall survival (OS), patients with low expression of miR-3065-5p had a median OS of 70 months, while patients with high levels did not reach the median OS (p = 0.041). Male patients with low expression of this miRNA had an OS of 70 months, whereas patients with high levels did not reach the median OS (p = 0.050). Under uni-multivariate analysis, clinical stage (HR: 1.30, CI 1.23–2.30; p: 0.001) and low levels of miR-3065-5p (HR: 1.30, CI 1.23–2.30; p: 0.001) were determined as predictor factors of OS. To this end, we designed the “Prognosis miRNAs assessment in cancer” (PROMIR-C) algorithm, which integrated clinical features with miR-3065-5p expression levels. Conclusions: These findings support the clinical utility of miR-26a-5p and miR-3065-5p in the diagnosis and prognosis of CRC. PROMIR-C is a fundamental tool for clinicians in treatment decision-making, prognosis assessment, and outcome of CRC. Full article
(This article belongs to the Special Issue Feature Papers in Section "Cancer Biomarkers" in 2023–2024)
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16 pages, 1514 KiB  
Article
Cobalt Serum Level as a Biomarker of Cause-Specific Survival among Prostate Cancer Patients
by Sandra Pietrzak, Wojciech Marciniak, Róża Derkacz, Milena Matuszczak, Adam Kiljańczyk, Piotr Baszuk, Marta Bryśkiewicz, Andrzej Sikorski, Jacek Gronwald, Marcin Słojewski, Cezary Cybulski, Adam Gołąb, Tomasz Huzarski, Tadeusz Dębniak, Marcin R. Lener, Anna Jakubowska, Tomasz Kluz, Marianna Soroka, Rodney J. Scott and Jan Lubiński
Cancers 2024, 16(15), 2618; https://doi.org/10.3390/cancers16152618 - 23 Jul 2024
Viewed by 1163
Abstract
Prostate cancer is the most common cancer diagnosed in men and the second leading cause of death in male cancer patients. The WHO suggests that cobalt is involved in the carcinogenesis of prostate cancer. There are, however, no studies associating cobalt levels and [...] Read more.
Prostate cancer is the most common cancer diagnosed in men and the second leading cause of death in male cancer patients. The WHO suggests that cobalt is involved in the carcinogenesis of prostate cancer. There are, however, no studies associating cobalt levels and prostate cancer patient survival. In this study, 261 Polish prostate cancer (n = 261) patients were recruited into a prospective cohort between 2009 and 2015. Serum cobalt levels were measured using ICP-MS after prostate cancer diagnosis and before treatment. All study participants were assigned into quartiles (QI-QIV) based on the distribution of serum cobalt levels among censored patients. Univariable and multivariable COX regression models were used to calculate hazard ratios (HRs) for each serum cobalt level quartile. We found a significant relationship between high serum cobalt levels and poor prostate cancer patient total survival (HR = 2.60; 95% CI: 1.17–5.82; p = 0.02). In relation to prostate cancer patients who died as a result of other non-cancer causes, the association with high levels of cobalt was even stronger (HR = 3.67; 95% CI: 1.03–13.00; p = 0.04). The impact of high serum cobalt levels on overall survival of prostate cancer-specific-related deaths was not statistically significant. Full article
(This article belongs to the Special Issue Feature Papers in Section "Cancer Biomarkers" in 2023–2024)
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15 pages, 2034 KiB  
Article
Circulating Tumor DNA Predicts Early Recurrence Following Locoregional Therapy for Oligometastatic Colorectal Cancer
by Conor D. J. O’Donnell, Nikolas Naleid, Teerada Siripoon, Kevin G. Zablonski, Michael H. Storandt, Jennifer E. Selfridge, Christopher L. Hallemeier, Madison L. Conces, Krishan R. Jethwa, David L. Bajor, Cornelius A. Thiels, Susanne G. Warner, Patrick P. Starlinger, Thomas D. Atwell, Jessica L. Mitchell, Amit Mahipal and Zhaohui Jin
Cancers 2024, 16(13), 2407; https://doi.org/10.3390/cancers16132407 - 29 Jun 2024
Viewed by 1381
Abstract
(1) Background: Local therapies offer a potentially curative approach for patients with oligometastatic colorectal cancer (CRC). An evidence-based consensus recommendation for systemic therapy following definitive locoregional therapy is lacking. Tumor-informed circulating tumor DNA (ctDNA) might provide information to help guide management in this [...] Read more.
(1) Background: Local therapies offer a potentially curative approach for patients with oligometastatic colorectal cancer (CRC). An evidence-based consensus recommendation for systemic therapy following definitive locoregional therapy is lacking. Tumor-informed circulating tumor DNA (ctDNA) might provide information to help guide management in this setting. (2) Methods: A multi-institutional retrospective study was conducted, including patients with CRC that underwent curative-intent locoregional therapy to an isolated site of metastatic disease, followed by tumor-informed ctDNA assessment. The Kaplan–Meier method and log-rank tests were used to compare disease-free survival based on ctDNA results. ctDNA test performance was compared to carcinoembryonic antigen (CEA) test results using McNemar’s test. (3) Results: Our study cohort consisted of 87 patients treated with locoregional interventions who underwent ctDNA testing. The initial ctDNA test post-intervention was positive in 28 patients and negative in 59 patients. The median follow-up time was 14.0 months. Detectable ctDNA post-intervention was significantly associated with early disease recurrence, with a median disease-free survival (DFS) of 6.63 months compared to 21.30 months in ctDNA-negative patients (p < 0.001). ctDNA detected a numerically higher proportion of recurrences than CEA (p < 0.097). Post-intervention systemic therapy was not associated with improved DFS (p = 0.745). (4) Conclusions: ctDNA results are prognostically important in oligometastatic CRC, and further prospective studies are urgently needed to define its role in guiding clinical decisions. Full article
(This article belongs to the Special Issue Feature Papers in Section "Cancer Biomarkers" in 2023–2024)
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13 pages, 2179 KiB  
Article
Transcript-Level Biomarkers of Early Lung Carcinogenesis in Bronchial Lesions
by Mikhail A. Pyatnitskiy and Ekaterina V. Poverennaya
Cancers 2024, 16(12), 2260; https://doi.org/10.3390/cancers16122260 - 18 Jun 2024
Viewed by 1036
Abstract
Premalignant lesions within the bronchial epithelium signify the initial phases of squamous cell lung carcinoma, posing challenges for detection via conventional methods. Instead of focusing solely on gene expression, in this study, we explore transcriptomic alterations linked to lesion progression, with an emphasis [...] Read more.
Premalignant lesions within the bronchial epithelium signify the initial phases of squamous cell lung carcinoma, posing challenges for detection via conventional methods. Instead of focusing solely on gene expression, in this study, we explore transcriptomic alterations linked to lesion progression, with an emphasis on protein-coding transcripts. We reanalyzed a publicly available RNA-Seq dataset on airway epithelial cells from 82 smokers with and without premalignant lesions. Transcript and gene abundance were quantified using kallisto, while differential expression and transcript usage analysis was performed utilizing sleuth and RATs packages. Functional characterization involved overrepresentation analysis via clusterProfiler, weighted coexpression network analysis (WGCNA), and network analysis via Enrichr-KG. We detected 5906 differentially expressed transcripts and 4626 genes, exhibiting significant enrichment within pathways associated with oxidative phosphorylation and mitochondrial function. Remarkably, transcript-level WGCNA revealed a single module correlated with dysplasia status, notably enriched in cilium-related biological processes. Notable hub transcripts included RABL2B (ENST00000395590), DNAH1 (ENST00000420323), EFHC1 (ENST00000635996), and VWA3A (ENST00000563389) along with transcription factors such as FOXJ1 and ZNF474 as potential regulators. Our findings underscore the value of transcript-level analysis in uncovering novel insights into premalignant bronchial lesion biology, including identification of potential biomarkers associated with early lung carcinogenesis. Full article
(This article belongs to the Special Issue Feature Papers in Section "Cancer Biomarkers" in 2023–2024)
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17 pages, 2758 KiB  
Article
Microsatellite Instability Testing and Prognostic Implications in Colorectal Cancer
by Vincent Ho, Liping Chung, Kate Wilkinson, Yafeng Ma, Tristan Rutland, Vivienne Lea, Stephanie H. Lim, Askar Abubakar, Weng Ng, Mark Lee, Tara L. Roberts, Therese M. Becker, Scott Mackenzie, Wei Chua and Cheok Soon Lee
Cancers 2024, 16(11), 2005; https://doi.org/10.3390/cancers16112005 - 25 May 2024
Viewed by 1415
Abstract
Given the crucial predictive implications of microsatellite instability (MSI) in colorectal cancer (CRC), MSI screening is commonly performed in those with and at risk for CRC. Here, we compared results from immunohistochemistry (IHC) and the droplet digital PCR (ddPCR) MSI assay on formalin-fixed [...] Read more.
Given the crucial predictive implications of microsatellite instability (MSI) in colorectal cancer (CRC), MSI screening is commonly performed in those with and at risk for CRC. Here, we compared results from immunohistochemistry (IHC) and the droplet digital PCR (ddPCR) MSI assay on formalin-fixed paraffin-embedded tumor samples from 48 patients who underwent surgery for colon and rectal cancer by calculating Cohen’s kappa measurement (k), revealing high agreement between the methods (k = 0.915). We performed Kaplan–Meier survival analyses and univariate and multivariate Cox regression to assess the prognostic significance of ddPCR-based MSI and to identify clinicopathological features associated with CRC outcome. Patients with MSI-high had better overall survival (OS; p = 0.038) and disease-free survival (DFS; p = 0.049) than those with microsatellite stability (MSS). When stratified by primary tumor location, right-sided CRC patients with MSI-high showed improved DFS, relative to those with MSS (p < 0.001), but left-sided CRC patients did not. In multivariate analyses, MSI-high was associated with improved OS (hazard ratio (HR) = 0.221, 95% confidence interval (CI): 0.026–0.870, p = 0.042), whereas the loss of DNA mismatch repair protein MutL homolog 1 (MLH1) expression was associated with worse OS (HR = 0.133, 95% CI: 0.001–1.152, p = 0.049). Our results suggest ddPCR is a promising tool for MSI detection. Given the opposing effects of MSI-high and MLH1 loss on OS, both ddPCR and IHC may be complementary for the prognostic assessment of CRC. Full article
(This article belongs to the Special Issue Feature Papers in Section "Cancer Biomarkers" in 2023–2024)
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Review

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28 pages, 2602 KiB  
Review
FOXM1 Transcriptionally Co-Upregulates Centrosome Amplification and Clustering Genes and Is a Biomarker for Poor Prognosis in Androgen Receptor-Low Triple-Negative Breast Cancer
by Padmashree Rida, Sophia Baker, Adam Saidykhan, Isabelle Bown and Nikita Jinna
Cancers 2024, 16(18), 3191; https://doi.org/10.3390/cancers16183191 - 18 Sep 2024
Viewed by 1119
Abstract
There are currently no approved targeted treatments for quadruple-negative breast cancer [QNBC; ER−/PR−/HER2−/androgen receptor (AR)−], a subtype of triple-negative breast cancer (TNBC). AR-low TNBC is more proliferative and clinically aggressive than AR-high TNBC. Centrosome amplification [...] Read more.
There are currently no approved targeted treatments for quadruple-negative breast cancer [QNBC; ER−/PR−/HER2−/androgen receptor (AR)−], a subtype of triple-negative breast cancer (TNBC). AR-low TNBC is more proliferative and clinically aggressive than AR-high TNBC. Centrosome amplification (CA), a cancer hallmark, is rampant in TNBC, where it induces spindle multipolarity-mediated cell death unless centrosome clustering pathways are co-upregulated to avert these sequelae. We recently showed that genes that confer CA and centrosome clustering are strongly overexpressed in AR-low TNBCs relative to AR-high TNBCs. However, the molecular mechanisms that index centrosome clustering to the levels of CA are undefined. We argue that FOXM1, a cell cycle-regulated oncogene, links the expression of genes that drive CA to the expression of genes that act at kinetochores and along microtubules to facilitate centrosome clustering. We provide compelling evidence that upregulation of the FOXM1-E2F1-ATAD2 oncogene triad in AR-low TNBC is accompanied by CA and the co-upregulation of centrosome clustering proteins such as KIFC1, AURKB, BIRC5, and CDCA8, conferring profound dysregulation of cell cycle controls. Targeting FOXM1 in AR-low TNBC may render cancer cells incapable of clustering their centrosomes and impair their ability to generate excess centrosomes. Hence, our review illuminates FOXM1 as a potential actionable target for AR-low TNBC. Full article
(This article belongs to the Special Issue Feature Papers in Section "Cancer Biomarkers" in 2023–2024)
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