Cancers

11 pages, 2324 KiB

Open AccessArticle

A Real-World Comparative Analysis of Atezolizumab Plus Bevacizumab and Transarterial Chemoembolization Plus Radiotherapy in Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombosis

by Soon Kyu Lee, Jung Hyun Kwon, Sung Won Lee, Hae Lim Lee, Hee Yeon Kim, Chang Wook Kim, Do Seon Song, U Im Chang, Jin Mo Yang, Soon Woo Nam, Seok-Hwan Kim, Myeong Jun Song, Ji Hoon Kim, Ahlim Lee, Hyun Yang, Si Hyun Bae, Ji Won Han, Heechul Nam, Pil Soo Sung, Jeong Won Jang, Jong Young Choi, Seung Kew Yoon, Dong Jae Shim, Doyoung Kim and Myungsoo Kim Show full author list Hide full author list

Cancers 2023, 15(17), 4423; https://doi.org/10.3390/cancers15174423 - 4 Sep 2023

Cited by 5 | Viewed by 1972

Abstract

This study aimed to compare the treatment outcomes of atezolizumab-plus-bevacizumab (Ate/Bev) therapy with those of transarterial chemoembolization plus radiotherapy (TACE + RT) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) and without metastasis. Between June 2016 and October 2022, we [...] Read more.

This study aimed to compare the treatment outcomes of atezolizumab-plus-bevacizumab (Ate/Bev) therapy with those of transarterial chemoembolization plus radiotherapy (TACE + RT) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) and without metastasis. Between June 2016 and October 2022, we consecutively enrolled 855 HCC patients with PVTT. After excluding 758 patients, 97 patients (n = 37 in the Ate/Bev group; n = 60 in the TACE + RT group) were analyzed. The two groups showed no significant differences in baseline characteristics and had similar objective response and disease control rates. However, the Ate/Bev group showed a significantly higher one-year survival rate (p = 0.041) compared to the TACE + RT group, which was constantly displayed in patients with extensive HCC burden. Meanwhile, the clinical outcomes were comparable between the two groups in patients with unilobar intrahepatic HCC. In Cox-regression analysis, Ate/Bev treatment emerged as a significant factor for better one-year survival (p = 0.049). Finally, in propensity-score matching, the Ate/Bev group demonstrated a better one-year survival (p = 0.02) and PFS (p = 0.01) than the TACE + RT group. In conclusion, Ate/Bev treatment demonstrated superior clinical outcomes compared to TACE + RT treatment in HCC patients with PVTT. Meanwhile, in patients with unilobar intrahepatic HCC, TACE + RT could also be considered as an alternative treatment option alongside Ate/Bev therapy. Full article

(This article belongs to the Collection Treatment of Hepatocellular Carcinoma and Cholangiocarcinoma)

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20 pages, 11248 KiB

Open AccessArticle

Novel Function of Cancer Stem Cell Marker ALDH1A3 in Glioblastoma: Pro-Angiogenesis through Paracrine PAI-1 and IL-8

by Zhen Chen, Rainer Will, Su Na Kim, Maike Anna Busch, Nicole Dünker, Philipp Dammann, Ulrich Sure and Yuan Zhu

Cancers 2023, 15(17), 4422; https://doi.org/10.3390/cancers15174422 - 4 Sep 2023

Cited by 3 | Viewed by 2010

Abstract

Hyper-angiogenesis is a typical feature of glioblastoma (GBM), the most aggressive brain tumor. We have reported the expression of aldehyde dehydrogenase 1A3 (ALDH1A3) in proliferating vasculature in GBM patients. We hypothesized that ALDH1A3 may act as an angiogenesis promoter in GBM. Two GBM [...] Read more.

Hyper-angiogenesis is a typical feature of glioblastoma (GBM), the most aggressive brain tumor. We have reported the expression of aldehyde dehydrogenase 1A3 (ALDH1A3) in proliferating vasculature in GBM patients. We hypothesized that ALDH1A3 may act as an angiogenesis promoter in GBM. Two GBM cell lines were lentivirally transduced with either ALDH1A3 (ox) or an empty vector (ev). The angiogenesis phenotype was studied in indirect and direct co-culture of endothelial cells (ECs) with oxGBM cells (oxGBMs) and in an angiogenesis model in vivo. Angiogenesis array was performed in oxGBMs. RT²-PCR, Western blot, and double-immunofluorescence staining were performed to confirm the expression of targets identified from the array. A significantly activated angiogenesis phenotype was observed in ECs indirectly and directly co-cultured with oxGBMs and in vivo. Overexpression of ALDH1A3 (oxALDH1A3) led to a marked upregulation of PAI-1 and IL-8 mRNA and protein and a consequential increased release of both proteins. Moreover, oxALDH1A3-induced angiogenesis was abolished by the treatment of the specific inhibitors, respectively, of PAI-1 and IL-8 receptors, CXCR1/2. This study defined ALDH1A3 as a novel angiogenesis promoter. oxALDH1A3 in GBM cells stimulated EC angiogenesis via paracrine upregulation of PAI-1 and IL-8, suggesting ALDH1A3-PAI-1/IL-8 as a novel signaling for future anti-angiogenesis therapy in GBM. Full article

(This article belongs to the Special Issue Glioblastoma: Recent Advances and Challenges)

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20 pages, 6576 KiB

Open AccessArticle

mAb14, a Monoclonal Antibody against Cell Surface PCNA: A Potential Tool for Sezary Syndrome Diagnosis and Targeted Immunotherapy

by Jamal Knaneh, Emmilia Hodak, Shlomit Fedida-Metula, Avishay Edri, Rachel Eren, Yael Yoffe, Iris Amitay-Laish, Hadas Prag Naveh, Ido Lubin, Angel Porgador and Lilach Moyal

Cancers 2023, 15(17), 4421; https://doi.org/10.3390/cancers15174421 - 4 Sep 2023

Cited by 2 | Viewed by 3310

Abstract

Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common types of primary cutaneous T-cell lymphoma (CTCL). Proliferating cell nuclear antigen (PCNA) is expressed on the cell surface of cancer cells (csPCNA), but not on normal cells. It functions as an immune [...] Read more.

Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common types of primary cutaneous T-cell lymphoma (CTCL). Proliferating cell nuclear antigen (PCNA) is expressed on the cell surface of cancer cells (csPCNA), but not on normal cells. It functions as an immune checkpoint ligand by interacting with natural killer (NK) cells through the NK inhibitory receptor NKp44, leading to the inhibition of NK cytotoxicity. A monoclonal antibody (mAb14) was established to detect csPCNA on cancer cells and block their interaction with NKp44. In this study, three CTCL cell lines and peripheral blood mononuclear cells (PBMCs) from patients with SS and healthy donors were analyzed for csPCNA using mAb14, compared to monoclonal antibody PC10, against nuclear PCNA (nPCNA). The following assays were used: immunostaining, imaging flow cytometry, flow cytometry, cell sorting, cell cycle analysis, ELISA, and the NK-cell cytotoxic assay. mAb14 successfully detected PCNA on the membrane and in the cytoplasm of viable CTCL cell lines associated with the G2/M phase. In the Sézary PBMCs, csPCNA was expressed on lymphoma cells that had an atypical morphology and not on normal cells. Furthermore, it was not expressed on PBMCs from healthy donors. In the co-culture of peripheral blood NK (pNK) cells with CTCL lines, mAb14 increased the secretion of IFN-γ, indicating the reactivation of pNK activity. However, mAb14 did not enhance the cytotoxic activity of pNK cells against CTCL cell lines. The unique expression of csPCNA detected by mAb14 suggests that csPCNA and mAb14 may serve as a potential biomarker and tool, respectively, for detecting malignant cells in SS and possibly other CTCL variants. Full article

(This article belongs to the Special Issue Advances in Immunotherapy for Hematological Malignancies)

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19 pages, 9336 KiB

Open AccessArticle

Differentially Expressed Genes, miRNAs and Network Models: A Strategy to Shed Light on Molecular Interactions Driving HNSCC Tumorigenesis

by Saniya Arfin, Dhruv Kumar, Andrea Lomagno, Pietro Luigi Mauri and Dario Di Silvestre

Cancers 2023, 15(17), 4420; https://doi.org/10.3390/cancers15174420 - 4 Sep 2023

Cited by 3 | Viewed by 2346

Abstract

Head and neck squamous cell carcinoma (HNSCC) is among the most common cancer worldwide, accounting for hundreds thousands deaths annually. Unfortunately, most patients are diagnosed in an advanced stage and only a percentage respond favorably to therapies. To help fill this gap, we [...] Read more.

Head and neck squamous cell carcinoma (HNSCC) is among the most common cancer worldwide, accounting for hundreds thousands deaths annually. Unfortunately, most patients are diagnosed in an advanced stage and only a percentage respond favorably to therapies. To help fill this gap, we hereby propose a retrospective in silico study to shed light on gene–miRNA interactions driving the development of HNSCC. Moreover, to identify topological biomarkers as a source for designing new drugs. To achieve this, gene and miRNA profiles from patients and controls are holistically reevaluated using protein–protein interaction (PPI) and bipartite miRNA–target networks. Cytoskeletal remodeling, extracellular matrix (ECM), immune system, proteolysis, and energy metabolism have emerged as major functional modules involved in the pathogenesis of HNSCC. Of note, the landscape of our findings depicts a concerted molecular action in activating genes promoting cell cycle and proliferation, and inactivating those suppressive. In this scenario, genes, including VEGFA, EMP1, PPL, KRAS, MET, TP53, MMPs and HOXs, and miRNAs, including mir-6728 and mir-99a, emerge as key players in the molecular interactions driving HNSCC tumorigenesis. Despite the heterogeneity characterizing these HNSCC subtypes, and the limitations of a study pointing to relationships that could be context dependent, the overlap with previously published studies is encouraging. Hence, it supports further investigation for key molecules, both those already and not correlated to HNSCC. Full article

(This article belongs to the Special Issue Genomics and Bioinformatics Based Analysis of Cancer)

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39 pages, 10589 KiB

Open AccessReview

Human Aldehyde Dehydrogenases: A Superfamily of Similar Yet Different Proteins Highly Related to Cancer

by Vasileios Xanthis, Theodora Mantso, Anna Dimtsi, Aglaia Pappa and Vasiliki E. Fadouloglou

Cancers 2023, 15(17), 4419; https://doi.org/10.3390/cancers15174419 - 4 Sep 2023

Cited by 5 | Viewed by 3741

Abstract

The superfamily of human aldehyde dehydrogenases (hALDHs) consists of 19 isoenzymes which are critical for several physiological and biosynthetic processes and play a major role in the organism’s detoxification via the NAD(P) dependent oxidation of numerous endogenous and exogenous aldehyde substrates to their [...] Read more.

The superfamily of human aldehyde dehydrogenases (hALDHs) consists of 19 isoenzymes which are critical for several physiological and biosynthetic processes and play a major role in the organism’s detoxification via the NAD(P) dependent oxidation of numerous endogenous and exogenous aldehyde substrates to their corresponding carboxylic acids. Over the last decades, ALDHs have been the subject of several studies as it was revealed that their differential expression patterns in various cancer types are associated either with carcinogenesis or promotion of cell survival. Here, we attempt to provide a thorough review of hALDHs’ diverse functions and 3D structures with particular emphasis on their role in cancer pathology and resistance to chemotherapy. We are especially interested in findings regarding the association of structural features and their changes with effects on enzymes’ functionalities. Moreover, we provide an updated outline of the hALDHs inhibitors utilized in experimental or clinical settings for cancer therapy. Overall, this review aims to provide a better understanding of the impact of ALDHs in cancer pathology and therapy from a structural perspective. Full article

(This article belongs to the Special Issue Protein Structure and Cancer)

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21 pages, 3702 KiB

Open AccessArticle

Primary Colorectal Tumor Displays Differential Genomic Expression Profiles Associated with Hepatic and Peritoneal Metastases

by Maximiliano Gelli, Christophe Desterke, Mohamed Amine Bani, Valérie Boige, Charles Ferté, Peggy Dartigues, Bastien Job, Geraldine Perkins, Pierre Laurent-Puig, Diane Goéré, Jacques R. R. Mathieu, Jerome Cartry, Michel Ducreux and Fanny Jaulin

Cancers 2023, 15(17), 4418; https://doi.org/10.3390/cancers15174418 - 4 Sep 2023

Cited by 1 | Viewed by 1804

Abstract

Background: Despite improvements in characterization of CRC heterogeneity, appropriate risk stratification tools are still lacking in clinical practice. This study aimed to elucidate the primary tumor transcriptomic signatures associated with distinct metastatic routes. Methods: Primary tumor specimens obtained from CRC patients with either [...] Read more.

Background: Despite improvements in characterization of CRC heterogeneity, appropriate risk stratification tools are still lacking in clinical practice. This study aimed to elucidate the primary tumor transcriptomic signatures associated with distinct metastatic routes. Methods: Primary tumor specimens obtained from CRC patients with either isolated LM (CRC-Liver) or PM (CRC-Peritoneum) were analyzed by transcriptomic mRNA sequencing, gene set enrichment analyses (GSEA) and immunohistochemistry. We further assessed the clinico-pathological associations and prognostic value of our signature in the COAD-TCGA independent cohort. Results: We identified a significantly different distribution of Consensus Molecular Subtypes between CRC-Liver and CRC-peritoneum groups. A transcriptomic signature based on 61 genes discriminated between liver and peritoneal metastatic routes. GSEA showed a higher expression of immune response and epithelial invasion pathways in CRC-Peritoneum samples and activation of proliferation and metabolic pathways in CRC-Liver samples. The biological relevance of RNA-Seq results was validated by the immunohistochemical expression of three significantly differentially expressed genes (ACE2, CLDN18 and DUSP4) in our signature. In silico analysis of the COAD-TCGA showed that the CRC-Peritoneum signature was associated with negative prognostic factors and poor overall and disease-free survivals. Conclusions: CRC primary tumors spreading to the liver and peritoneum display significantly different transcriptomic profiles. The implementation of this signature in clinical practice could contribute to identify new therapeutic targets for stage IV CRC and to define individualized follow-up programs in stage II-III CRC. Full article

(This article belongs to the Special Issue Signaling Pathway in Gastrointestinal Cancer)

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15 pages, 1366 KiB

Open AccessArticle

Differences in the Clinical and Molecular Profiles of Subungual Melanoma and Acral Melanoma in Asian Patients

by So-Young Ahn, Go-Eun Bae, Seung-Yeol Park and Min-Kyung Yeo

Cancers 2023, 15(17), 4417; https://doi.org/10.3390/cancers15174417 - 4 Sep 2023

Cited by 2 | Viewed by 1366

Abstract

Subungual melanoma (SUM) is a rare type of malignant melanoma that arises beneath the nails. SUM is categorized as a type of acral melanoma (AM), which occurs on the hands and feet. SUM is an aggressive type of cutaneous melanoma that is most [...] Read more.

Subungual melanoma (SUM) is a rare type of malignant melanoma that arises beneath the nails. SUM is categorized as a type of acral melanoma (AM), which occurs on the hands and feet. SUM is an aggressive type of cutaneous melanoma that is most common among Asian patients. Recent studies reveal that SUM and AM might have different molecular characteristics. Treatment of melanoma relies on analysis of both clinical and molecular data. Therefore, the clinical and molecular characteristics of SUM need to be established, especially during metastasis. To define the mutation profiles of SUM and compare them with those of AM, we performed next-generation sequencing of primary and metastatic tumors of SUM and AM patients. Subungual location was a better independent prognostic factor than acral location for better overall survival (p = 0.001). Patients with SUM most commonly had the triple wild-type (75%) driven by GNAQ (58%) and KIT (25%) mutations, whereas patients with AM had BRAF (28.6%) and RAF (14.3%) molecular types of mutations. Single-nucleotide variations (SNVs) were more common in SUM than in AM, whereas copy number alterations (CNAs) were more common metastatic lesions of AM. Metastatic tumors in patients with SUM and AM showed increases in CNAs (43% and 80%, respectively), but not in SNVs. The number of CNAs increased during metastasis. When compared with AM, SUM has distinct clinical and molecular characteristics. Full article

(This article belongs to the Special Issue Clinico-Pathological, Dermoscopic and Genetic Analyses in Melanoma: Different Diagnostic Processes for an Early and Accurate Detection of Melanoma)

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14 pages, 2841 KiB

Open AccessArticle

Genomic Alterations Associated with Estrogen Receptor Pathway Activity in Metastatic Breast Cancer Have a Differential Impact on Downstream ER Signaling

by Lindsay Angus, Marcel Smid, Saskia M. Wilting, Manouk K. Bos, Neeltje Steeghs, Inge R. H. M. Konings, Vivianne C. G. Tjan-Heijnen, Johanna M. G. H. van Riel, Agnes J. van de Wouw, CPCT Consortium, Edwin Cuppen, Martijn P. Lolkema, Agnes Jager, Stefan Sleijfer and John W. M. Martens

Cancers 2023, 15(17), 4416; https://doi.org/10.3390/cancers15174416 - 4 Sep 2023

Cited by 1 | Viewed by 1696

Abstract

Mutations in the estrogen receptor gene (ESR1), its transcriptional regulators, and the mitogen-activated protein kinase (MAPK) pathway are enriched in patients with endocrine-resistant metastatic breast cancer (MBC). Here, we integrated whole genome sequencing with RNA sequencing data from the same samples [...] Read more.

Mutations in the estrogen receptor gene (ESR1), its transcriptional regulators, and the mitogen-activated protein kinase (MAPK) pathway are enriched in patients with endocrine-resistant metastatic breast cancer (MBC). Here, we integrated whole genome sequencing with RNA sequencing data from the same samples of 101 ER-positive/HER2-negative MBC patients who underwent a tumor biopsy prior to the start of a new line of treatment for MBC (CPCT-02 study, NCT01855477) to analyze the downstream effects of DNA alterations previously linked to endocrine resistance, thereby gaining a better understanding of the associated mechanisms. Hierarchical clustering was performed using expression of ESR1 target genes. Genomic alterations at the DNA level, gene expression levels, and last administered therapy were compared between the identified clusters. Hierarchical clustering revealed two distinct clusters, one of which was characterized by increased expression of ESR1 and its target genes. Samples in this cluster were significantly enriched for mutations in ESR1 and amplifications in FGFR1 and TSPYL. Patients in the other cluster showed relatively lower expression levels of ESR1 and its target genes, comparable to ER-negative samples, and more often received endocrine therapy as their last treatment before biopsy. Genes in the MAPK-pathway, including NF1, and ESR1 transcriptional regulators were evenly distributed. In conclusion, RNA sequencing identified a subgroup of patients with clear expression of ESR1 and its downstream targets, probably still benefiting from ER-targeting agents. The lower ER expression in the other subgroup might be partially explained by ER activity still being blocked by recently administered endocrine treatment, indicating that biopsy timing relative to endocrine treatment needs to be considered when interpreting transcriptomic data. Full article

(This article belongs to the Special Issue Estrogens and Estrogen Receptor Modulators in Cancer Research and Therapy)

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9 pages, 937 KiB

Open AccessArticle

Radiomics-Based Prediction of TERT Promotor Mutations in Intracranial High-Grade Meningiomas

by Burak Han Akkurt, Dorothee Cäcilia Spille, Susanne Peetz-Dienhart, Nora Maren Kiolbassa, Christian Mawrin, Manfred Musigmann, Walter Leonhard Heindel, Werner Paulus, Walter Stummer, Manoj Mannil and Benjamin Brokinkel

Cancers 2023, 15(17), 4415; https://doi.org/10.3390/cancers15174415 - 4 Sep 2023

Viewed by 1408

Abstract

Purpose: In meningiomas, TERT promotor mutations are rare but qualify the diagnosis of anaplasia, directly impacting adjuvant therapy. Effective screening for patients at risk for promotor mutations could enable more targeted molecular analyses and improve diagnosis and treatment. Methods: Semiautomatic segmentation of intracranial [...] Read more.

Purpose: In meningiomas, TERT promotor mutations are rare but qualify the diagnosis of anaplasia, directly impacting adjuvant therapy. Effective screening for patients at risk for promotor mutations could enable more targeted molecular analyses and improve diagnosis and treatment. Methods: Semiautomatic segmentation of intracranial grade 2/3 meningiomas was performed on preoperative magnetic resonance imaging. Discriminatory power to predict TERT promoter mutations was analyzed using a random forest algorithm with an increasing number of radiomic features. Two final models with five and eight features with both fixed and differing radiomics features were developed and adjusted to eliminate random effects and to avoid overfitting. Results: A total of 117 image sets including training (N = 94) and test data (N = 23) were analyzed. To eliminate random effects and demonstrate the robustness of our approach, data partitioning and subsequent model development and testing were repeated a total of 100 times (each time with repartitioned training and independent test data). The established five- and eight-feature models with both fixed and different radiomics features enabled the prediction of TERT with similar but excellent performance. The five-feature (different/fixed) model predicted TERT promotor mutation status with a mean AUC of 91.8%/94.3%, mean accuracy of 85.5%/88.9%, mean sensitivity of 88.6%/91.4%, mean specificity of 83.2%/87.0%, and a mean Cohen’s Kappa of 71.0%/77.7%. The eight-feature (different/fixed) model predicted TERT promotor mutation status with a mean AUC of 92.7%/94.6%, mean accuracy of 87.3%/88.9%, mean sensitivity of 89.6%/90.6%, mean specificity of 85.5%/87.5%, and a mean Cohen’s Kappa of 74.4%/77.6%. Of note, the addition of further features of up to N = 8 only slightly increased the performance. Conclusions: Radiomics-based machine learning enables prediction of TERT promotor mutation status in meningiomas with excellent discriminatory performance. Future analyses in larger cohorts should include grade 1 lesions as well as additional molecular alterations. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and the Management of Intracranial Tumors)

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23 pages, 1367 KiB

Open AccessArticle

Depression, Inflammation, and Intestinal Permeability: Associations with Subjective and Objective Cognitive Functioning throughout Breast Cancer Survivorship

by Annelise A. Madison, Rebecca Andridge, Anthony H. Kantaras, Megan E. Renna, Jeanette M. Bennett, Catherine M. Alfano, Stephen P. Povoski, Doreen M. Agnese, Maryam Lustberg, Robert Wesolowski, William E. Carson III, Nicole O. Williams, Raquel E. Reinbolt, Sagar D. Sardesai, Anne M. Noonan, Daniel G. Stover, Mathew A. Cherian, William B. Malarkey and Janice K. Kiecolt-Glaser

Cancers 2023, 15(17), 4414; https://doi.org/10.3390/cancers15174414 - 4 Sep 2023

Cited by 5 | Viewed by 2445

Abstract

About one-in-three breast cancer survivors have lingering cognitive complaints and objective cognitive impairment. Chronic inflammation and intestinal permeability (i.e., leaky gut), two risk factors for cognitive decline, can also fuel depression—another vulnerability for cognitive decline. The current study tested whether depression accompanied by [...] Read more.

About one-in-three breast cancer survivors have lingering cognitive complaints and objective cognitive impairment. Chronic inflammation and intestinal permeability (i.e., leaky gut), two risk factors for cognitive decline, can also fuel depression—another vulnerability for cognitive decline. The current study tested whether depression accompanied by high levels of inflammation or intestinal permeability predicted lower subjective and objective cognitive function in breast cancer survivors. We combined data from four breast cancer survivor studies (n = 613); some had repeated measurements for a total of 1015 study visits. All participants had a blood draw to obtain baseline measures of lipopolysaccharide binding protein—a measure of intestinal permeability, as well as three inflammatory markers that were incorporated into an inflammatory index: C-reactive protein, interleukin-6, and tumor necrosis factor-α. They reported depressive symptoms on the Center for Epidemiological Studies depression scale (CES-D), and a binary variable indicated clinically significant depressive symptoms (CES-D ≥ 16). The Kohli (749 observations) and the Breast Cancer Prevention Trial (591 observations) scales assessed subjective cognitive function. Objective cognitive function tests included the trail-making test, Hopkins verbal learning test, Conners continuous performance test, n-back test, FAS test, and animal-naming test (239–246 observations). Adjusting for education, age, BMI, cancer treatment type, time since treatment, study visit, and fatigue, women who had clinically elevated depressive symptoms accompanied by heightened inflammation or intestinal permeability reported poorer focus and marginally poorer memory. However, poorer performance across objective cognitive measures was not specific to inflammation-associated depression. Rather, there was some evidence of lower verbal fluency; poorer attention, verbal learning and memory, and working memory; and difficulties with visuospatial search among depressed survivors, regardless of inflammation. By themselves, inflammation and intestinal permeability less consistently predicted subjective or objective cognitive function. Breast cancer survivors with clinically significant depressive symptoms accompanied by either elevated inflammation or intestinal permeability may perceive greater cognitive difficulty, even though depression-related objective cognitive deficits may not be specific to inflammation- or leaky-gut-associated depression. Full article

(This article belongs to the Special Issue Cognitive Outcomes in Cancer: Recent Advances and Challenges)

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12 pages, 3425 KiB

Open AccessArticle

Can High-Frequency Intraoral Ultrasound Predict Histological Risk Factors in Oral Squamous Cell Carcinoma? A Preliminary Experience

by Simone Caprioli, Giorgio-Gregory Giordano, Alessia Pennacchi, Valentina Campagnari, Andrea Iandelli, Giampiero Parrinello, Cristina Conforti, Riccardo Gili, Edoardo Giannini, Elisa Marabotto, Stefano Kayali, Bernardo Bianchi, Giorgio Peretti, Giuseppe Cittadini and Filippo Marchi

Cancers 2023, 15(17), 4413; https://doi.org/10.3390/cancers15174413 - 4 Sep 2023

Cited by 3 | Viewed by 1359

Abstract

Despite advancements in multidisciplinary care, oncologic outcomes of oral cavity squamous cell carcinoma (OSCC) have not substantially improved: still, one-third of patients affected by stage I and II can develop locoregional recurrences. Imaging plays a pivotal role in preoperative staging of OSCC, providing [...] Read more.

Despite advancements in multidisciplinary care, oncologic outcomes of oral cavity squamous cell carcinoma (OSCC) have not substantially improved: still, one-third of patients affected by stage I and II can develop locoregional recurrences. Imaging plays a pivotal role in preoperative staging of OSCC, providing depth of invasion (DOI) measurements. However, locoregional recurrences have a strong association with adverse histopathological factors not included in the staging system, and any imaging features linked to them have been lacking. In this study, the possibility to predict histological risk factors in OSCC with high-frequency intraoral ultrasonography (IOUS) was evaluated. Thirty-four patients were enrolled. The agreement between ultrasonographic and pathological DOI was evaluated, and ultrasonographic margins’ appearance was compared to the Brandwein-Gensler score and the worst pattern of invasion (WPOI). Excellent agreement between ultrasonographic and pathological DOI was found (mean difference: 0.2 mm). A significant relationship was found between ultrasonographic morphology of the front of infiltration and both Brandwein-Gensler score ≥ 3 (p < 0.0001) and WPOI ≥4 (p = 0.0001). Sensitivity, specificity, positive predictive value, and negative predictive value for the IOUS to predict a Brandwein-Gensler score ≥3 were 93.33%, 89.47%, 87.50%, and 94.44%, respectively. The present study demonstrated the promising role of IOUS in aiding risk stratification for OSCC patients. Full article

(This article belongs to the Special Issue Gastrointestinal Tract Cancers, an Increasing Burden of the Modern Era: Epidemiology and Prevention)

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19 pages, 571 KiB

Open AccessArticle

Improving Prediction of Cervical Cancer Using KNN Imputed SMOTE Features and Multi-Model Ensemble Learning Approach

by Hanen Karamti, Raed Alharthi, Amira Al Anizi, Reemah M. Alhebshi, Ala’ Abdulmajid Eshmawi, Shtwai Alsubai and Muhammad Umer

Cancers 2023, 15(17), 4412; https://doi.org/10.3390/cancers15174412 - 4 Sep 2023

Cited by 13 | Viewed by 2695

Abstract

Objective: Cervical cancer ranks among the top causes of death among females in developing countries. The most important procedures that should be followed to guarantee the minimizing of cervical cancer’s aftereffects are early identification and treatment under the finest medical guidance. One of [...] Read more.

Objective: Cervical cancer ranks among the top causes of death among females in developing countries. The most important procedures that should be followed to guarantee the minimizing of cervical cancer’s aftereffects are early identification and treatment under the finest medical guidance. One of the best methods to find this sort of malignancy is by looking at a Pap smear image. For automated detection of cervical cancer, the available datasets often have missing values, which can significantly affect the performance of machine learning models. Methods: To address these challenges, this study proposes an automated system for predicting cervical cancer that efficiently handles missing values with SMOTE features to achieve high accuracy. The proposed system employs a stacked ensemble voting classifier model that combines three machine learning models, along with KNN Imputer and SMOTE up-sampled features for handling missing values. Results: The proposed model achieves 99.99% accuracy, 99.99% precision, 99.99% recall, and 99.99% F1 score when using KNN imputed SMOTE features. The study compares the performance of the proposed model with multiple other machine learning algorithms under four scenarios: with missing values removed, with KNN imputation, with SMOTE features, and with KNN imputed SMOTE features. The study validates the efficacy of the proposed model against existing state-of-the-art approaches. Conclusions: This study investigates the issue of missing values and class imbalance in the data collected for cervical cancer detection and might aid medical practitioners in timely detection and providing cervical cancer patients with better care. Full article

(This article belongs to the Special Issue Artificial Intelligence in Cancer Screening)

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12 pages, 1476 KiB

Open AccessArticle

Genetic Regulation of Human isomiR Biogenesis

by Guanglong Jiang, Jill L. Reiter, Chuanpeng Dong, Yue Wang, Fang Fang, Zhaoyang Jiang and Yunlong Liu

Cancers 2023, 15(17), 4411; https://doi.org/10.3390/cancers15174411 - 4 Sep 2023

Viewed by 1491

Abstract

MicroRNAs play a critical role in regulating gene expression post-transcriptionally. Variations in mature microRNA sequences, known as isomiRs, arise from imprecise cleavage and nucleotide substitution or addition. These isomiRs can target different mRNAs or compete with their canonical counterparts, thereby expanding the scope [...] Read more.

MicroRNAs play a critical role in regulating gene expression post-transcriptionally. Variations in mature microRNA sequences, known as isomiRs, arise from imprecise cleavage and nucleotide substitution or addition. These isomiRs can target different mRNAs or compete with their canonical counterparts, thereby expanding the scope of miRNA post-transcriptional regulation. Our study investigated the relationship between cis-acting single-nucleotide polymorphisms (SNPs) in precursor miRNA regions and isomiR composition, represented by the ratio of a specific 5′-isomiR subtype to all isomiRs identified for a particular mature miRNA. Significant associations between 95 SNP–isomiR pairs were identified. Of note, rs6505162 was significantly associated with both the 5′-extension of hsa-miR-423-3p and the 5′-trimming of hsa-miR-423-5p. Comparison of breast cancer and normal samples revealed that the expression of both isomiRs was significantly higher in tumors than in normal tissues. This study sheds light on the genetic regulation of isomiR maturation and advances our understanding of post-transcriptional regulation by microRNAs. Full article

(This article belongs to the Section Molecular Cancer Biology)

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14 pages, 286 KiB

Open AccessEditor’s ChoiceArticle

Changes in the Number of Gastrointestinal Cancers and Stage at Diagnosis with COVID-19 Pandemic in Japan: A Multicenter Cohort Study

by Kento Kuzuu, Noboru Misawa, Keiichi Ashikari, Shigeki Tamura, Shingo Kato, Kunihiro Hosono, Masato Yoneda, Takashi Nonaka, Shozo Matsushima, Tatsuji Komatsu, Atsushi Nakajima and Takuma Higurashi

Cancers 2023, 15(17), 4410; https://doi.org/10.3390/cancers15174410 - 4 Sep 2023

Cited by 7 | Viewed by 1807

Abstract

This retrospective cohort study compared the number of newly diagnosed patients, stage at diagnosis, and detection process of gastrointestinal cancers based on hospital-based cancer registry data at two tertiary Japanese hospitals. The pre-COVID-19 period was from January 2017 to February 2020, with phase [...] Read more.

This retrospective cohort study compared the number of newly diagnosed patients, stage at diagnosis, and detection process of gastrointestinal cancers based on hospital-based cancer registry data at two tertiary Japanese hospitals. The pre-COVID-19 period was from January 2017 to February 2020, with phase 1 (midst of COVID-19 pandemic) from March to December 2020 and phase 2 (the transition period to the “new normal”) from January to December 2021. Each month, the number of patients diagnosed with esophageal, gastric, colorectal, pancreatic, liver, and biliary tract cancers were aggregated, classified by stage and detection process, and compared, including a total of 6453 patients. The number of colorectal Stage 0-II patients decreased significantly in phase 1 and increased in phase 2. The total number of colorectal cancer patients returned to pre-COVID-19 levels (mean monthly patients [SD]: 41.61 [6.81] vs. 36.00 [6.72] vs. 46.00 [11.32]). The number of patients with gastric cancer Stage I significantly decreased in phase 2 following phase 1. The number of gastric cancer patients decreased significantly from pre-COVID-19 levels (30.63 [6.62] vs. 22.40 [5.85] vs. 24.50 [4.15]). During phase 2, the number of patients diagnosed after screening with colorectal cancer increased significantly, whereas that with gastric cancer remained considerably lower. The number of Stage III colorectal and gastric cancer patients increased significantly from the pre-COVID-19 levels. Thus, gastric cancer may not be optimally screened during phases 1 and 2. There was a significant increase in patients with Stage III colorectal and gastric cancers from the pre-COVID-19 period; hence, the stage at diagnosis may have progressed. Full article

(This article belongs to the Collection The Impact of COVID-19 Infection in Cancer)

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26 pages, 3035 KiB

Open AccessReview

An Overview of Head and Neck Tumor Reirradiation: What Has Been Achieved So Far?

by Konstantin Gordon, Daniil Smyk, Igor Gulidov, Kirill Golubev and Timur Fatkhudinov

Cancers 2023, 15(17), 4409; https://doi.org/10.3390/cancers15174409 - 4 Sep 2023

Cited by 5 | Viewed by 2850

Abstract

The recurrence rate of head and neck cancers (HNCs) after initial treatment may reach 70%, and poor prognosis is reported in most cases. Curative options for recurrent HNCs mainly depend on the treatment history and the recurrent tumor localization. Reirradiation for HNCs is [...] Read more.

The recurrence rate of head and neck cancers (HNCs) after initial treatment may reach 70%, and poor prognosis is reported in most cases. Curative options for recurrent HNCs mainly depend on the treatment history and the recurrent tumor localization. Reirradiation for HNCs is effective and has been included in most guidelines. However, the option remains clinically challenging due to high incidence of severe toxicity, especially in cases of quick infield recurrence. Recent technical advances in radiation therapy (RT) provide the means for upgrade in reirradiation protocols. While the majority of hospitals stay focused on conventional and widely accessible modulated RTs, the particle therapy options emerge as tolerable and providing further treatment opportunities for recurrent HNCs. Still, the progress is impeded by high heterogeneity of the data and the lack of large-scale prospective studies. This review aimed to summarize the outcomes of reirradiation for HNCs in the clinical perspective. Full article

(This article belongs to the Section Cancer Therapy)

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15 pages, 1676 KiB

Open AccessArticle

Association of Fibrinolytic Potential and Risk of Mortality in Cancer Patients

by Gabriele Silva Souza Gois, Silmara Aparecida Lima Montalvão, Thaizy Ramires Alencar Anhaia, Millene Evelyn Alves Almeida, Beatriz Moraes Martinelli, Maria Carmen Gonçalves Lopes Fernandes, Stephany Cares Hubers, Monique R. M. Ferreira, Daniel Dias Ribeiro, Júlio César Teixeira, José Barreto Campello Carvalheira, Carmen Silvia Passos Lima, Nelson Adami Andreollo, Maurício Etchebehere, Lair Zambon, Ubirajara Ferreira, Alfio José Tincani, Antônio Santos Martins, Cláudio Saddy Rodrigues Coy, José Cláudio Teixeira Seabra, Ricardo Kalaf Mussi, Helder Tedeschi, Joyce Maria Anninchino-Bizzacchi and ADVENTH Cancer Group Show full author list Hide full author list

Cancers 2023, 15(17), 4408; https://doi.org/10.3390/cancers15174408 - 3 Sep 2023

Viewed by 1301

Abstract

Cancer is a leading cause of death, and the fibrinolytic system shows cooperative effects that facilitate the growth of tumors and the appearance of metastases. This prospective study aimed to evaluate the fibrinolytic potential in cancer patients and its association with mortality outcomes [...] Read more.

Cancer is a leading cause of death, and the fibrinolytic system shows cooperative effects that facilitate the growth of tumors and the appearance of metastases. This prospective study aimed to evaluate the fibrinolytic potential in cancer patients and its association with mortality outcomes using the fluorometric method of simultaneous thrombin and plasmin generation. The study included 323 cancer patients and 148 healthy individuals. During the 12-month follow-up, 68 patients died. Compared to the control group, cancer patients showed alterations in thrombin production consistent with a hypercoagulability profile, and an increase in plasmin generation. Mortality risk was associated with two parameters of thrombin in both univariate and multivariable analysis: maximum amplitude (Wald 11.78, p < 0.001) and area under the curve (Wald 8.0, p < 0.005), while such associations were not observed for plasmin. In conclusion, this was the first study able to demonstrate the simultaneous evaluation of thrombin and plasmin generation in newly diagnosed untreated cancer patients. Patients with cancer have been observed to exhibit a hypercoagulable profile. During the study, two parameters linked to thrombin generation, MA and AUC, were identified and found to have a potential association with mortality risk. However, no associations were found with parameters related to plasmin generation. Full article

(This article belongs to the Section Cancer Epidemiology and Prevention)

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13 pages, 1537 KiB

Open AccessArticle

Multi-omics Characterization of Response to PD-1 Inhibitors in Advanced Melanoma

by Lucía Trilla-Fuertes, Angelo Gámez-Pozo, Guillermo Prado-Vázquez, Rocío López-Vacas, Virtudes Soriano, Fernando Garicano, M. José Lecumberri, María Rodríguez de la Borbolla, Margarita Majem, Elisabeth Pérez-Ruiz, María González-Cao, Juana Oramas, Alejandra Magdaleno, Joaquín Fra, Alfonso Martín-Carnicero, Mónica Corral, Teresa Puértolas, Ricardo Ramos-Ruiz, Antje Dittmann, Paolo Nanni, Juan Ángel Fresno Vara and Enrique Espinosa Show full author list Hide full author list

Cancers 2023, 15(17), 4407; https://doi.org/10.3390/cancers15174407 - 3 Sep 2023

Cited by 2 | Viewed by 1818

Abstract

Immunotherapy improves the survival of patients with advanced melanoma, 40% of whom become long-term responders. However, not all patients respond to immunotherapy. Further knowledge of the processes involved in the response and resistance to immunotherapy is still needed. In this study, clinical paraffin [...] Read more.

Immunotherapy improves the survival of patients with advanced melanoma, 40% of whom become long-term responders. However, not all patients respond to immunotherapy. Further knowledge of the processes involved in the response and resistance to immunotherapy is still needed. In this study, clinical paraffin samples from fifty-two advanced melanoma patients treated with anti-PD-1 inhibitors were assessed via high-throughput proteomics and RNA-seq. The obtained proteomics and transcriptomics data were analyzed using multi-omics network analyses based on probabilistic graphical models to identify those biological processes involved in the response to immunotherapy. Additionally, proteins related to overall survival were studied. The activity of the node formed by the proteins involved in protein processing in the endoplasmic reticulum and antigen presentation machinery was higher in responders compared to non-responders; the activity of the immune and inflammatory response node was also higher in those with complete or partial responses. A predictor for overall survival based on two proteins (AMBP and PDSM5) was defined. In summary, the response to anti-PD-1 therapy in advanced melanoma is related to protein processing in the endoplasmic reticulum, and also to genes involved in the immune and inflammatory responses. Finally, a two-protein predictor can define survival in advanced disease. The molecular characterization of the mechanisms involved in the response and resistance to immunotherapy in melanoma leads the way to establishing therapeutic alternatives for patients who will not respond to this treatment. Full article

(This article belongs to the Section Cancer Immunology and Immunotherapy)

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19 pages, 3083 KiB

Open AccessArticle

High-Throughput Drug Screening Revealed That Ciclopirox Olamine Can Engender Gastric Cancer Stem-like Cells

by Diana Pádua, Paula Figueira, Mariana Pinto, André Filipe Maia, Joana Peixoto, Raquel T. Lima, António Pombinho, Carlos Filipe Pereira, Raquel Almeida and Patrícia Mesquita

Cancers 2023, 15(17), 4406; https://doi.org/10.3390/cancers15174406 - 3 Sep 2023

Cited by 1 | Viewed by 2822

Abstract

Cancer stem cells (CSCs) are relevant therapeutic targets for cancer treatment. Still, the molecular circuits behind CSC characteristics are not fully understood. The low number of CSCs can sometimes be an obstacle to carrying out assays that explore their properties. Thus, increasing CSC [...] Read more.

Cancer stem cells (CSCs) are relevant therapeutic targets for cancer treatment. Still, the molecular circuits behind CSC characteristics are not fully understood. The low number of CSCs can sometimes be an obstacle to carrying out assays that explore their properties. Thus, increasing CSC numbers via small molecule-mediated cellular reprogramming appears to be a valid alternative tool. Using the SORE6-GFP reporter system embedded in gastric non-CSCs (SORE6−), we performed a high-throughput image-based drug screen with 1200 small molecules to identify compounds capable of converting SORE6− to SORE6+ (CSCs). Here, we report that the antifungal agent ciclopirox olamine (CPX), a potential candidate for drug repurposing in cancer treatment, is able to reprogram gastric non-CSCs into cancer stem-like cells via activation of SOX2 expression and increased expression of C-MYC, HIF-1α, KLF4, and HMGA1. This reprogramming depends on the CPX concentration and treatment duration. CPX can also induce cellular senescence and the metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis. We also disclose that the mechanism underlying the cellular reprogramming is similar to that of cobalt chloride (CoCl₂), a hypoxia-mimetic agent. Full article

(This article belongs to the Section Cancer Drug Development)

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13 pages, 600 KiB

Open AccessSystematic Review

Squamous Cell Carcinoma of the Oral Cavity, Oropharynx, and Larynx: A Scoping Review of Treatment Guidelines Worldwide

by Lady Paola Aristizabal Arboleda, Genival Barbosa de Carvalho, Alan Roger Santos-Silva, Gisele Aparecida Fernandes, Jose Guilherme Vartanian, David I. Conway, Shama Virani, Paul Brennan, Luiz Paulo Kowalski and Maria Paula Curado

Cancers 2023, 15(17), 4405; https://doi.org/10.3390/cancers15174405 - 3 Sep 2023

Cited by 11 | Viewed by 3841

Abstract

Head and neck cancer (HNC) treatments have been based on single or multimodal therapies with surgery, radiotherapy (RT), chemotherapy, and immunotherapy. However, treatment recommendations among countries may differ due to technological/human resources and usual local practices. This scoping review aims to identify, compare, [...] Read more.

Head and neck cancer (HNC) treatments have been based on single or multimodal therapies with surgery, radiotherapy (RT), chemotherapy, and immunotherapy. However, treatment recommendations among countries may differ due to technological/human resources and usual local practices. This scoping review aims to identify, compare, and map the clinical practice guidelines (CPGs) for treating squamous cell carcinoma (SCC) of the oral cavity, oropharynx, and larynx worldwide. A search strategy on global CPGs for HNC was performed by using five electronic databases and grey literature. CPGs were selected for inclusion using EndNote-20 and Rayyan online software. No language or publication date restrictions were applied. The results were analyzed descriptively considering the most updated CPG version. In total, 25 CPGs covering the head and neck region (10), the larynx (7), the oral cavity (5), and the oropharynx (3), were found in 13 geographical regions, and 19 were developed by medical societies from 1996 to 2023. Surgery and RT remain the main modalities for early-stage HNC, with surgery preferred in low-resource countries, and RT in selected cases, especially in the larynx/oropharynx aiming to achieve a cure with organ preservation. Human papillomavirus infection for oropharyngeal SCC is not tested in some Asian countries and there is still no consensus to treat p16-positive cases differently from p16-negative. Recommendations for larynx preservation vary according to facilities in each country, however, individualized choice is emphasized. Inequality across countries/continents is evident, with a similar pattern of recommendations among developed as well as developing ones. No CPGs were found in Latin America as well as Oceania countries, where the incidence of HNC is high and limitations of access to treatment may be encountered. Full article

(This article belongs to the Special Issue Head and Neck Cancer: Epidemiology, Prevention, Treatment, and Quality of Life)

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15 pages, 869 KiB

Open AccessReview

PET/CT and Conventional Imaging for the Assessment of Neuroendocrine Prostate Cancer: A Systematic Review

by Francesco Dondi, Alessandro Antonelli, Nazareno Suardi, Andrea Emanuele Guerini, Domenico Albano, Silvia Lucchini, Luca Camoni, Giorgio Treglia and Francesco Bertagna

Cancers 2023, 15(17), 4404; https://doi.org/10.3390/cancers15174404 - 3 Sep 2023

Cited by 1 | Viewed by 1967

Abstract

Background: Neuroendocrine prostate cancer (NEPC) is a rare neoplasm, and the role of both conventional imaging (CI) and positron emission tomography/computed tomography (PET/CT) for its assessment has not been clearly evaluated and demonstrated. The aim of this systematic review was to analyze the [...] Read more.

Background: Neuroendocrine prostate cancer (NEPC) is a rare neoplasm, and the role of both conventional imaging (CI) and positron emission tomography/computed tomography (PET/CT) for its assessment has not been clearly evaluated and demonstrated. The aim of this systematic review was to analyze the diagnostic performances of these imaging modalities in this setting. Methods: A wide literature search of the PubMed/MEDLINE, Scopus, and Web of Science databases was made to find relevant published articles about the role of CI and PET/CT for the evaluation of NEPC. Results: 13 studies were included in the systematic review. PET/CT imaging with different radiopharmaceuticals has been evaluated in many studies (10) compared to CI (3 studies), which has only a limited role in NEPC. Focusing on PET/CT, a study used [¹⁸F]FDG, labeled somatostatin analogs were used in 5 cases, a study used [⁶⁸Ga]Ga-FAPI-04, [⁶⁸Ga]Ga-PSMA-11 was evaluated in a single case, and two works used different tracers. Conclusion: Published data on the role of PET/CT for the assessment of NEPC are limited. At present, it is still uncertain which tracer performs best, and although [¹⁸F]FDG has been evaluated and seems to offer some advantages in availability and clinical staging, other tracers may be more useful to understand tumor biology or identify targets for subsequent radioligand therapy. Further research is therefore desirable. In contrast, data are still limited to draw a final conclusion on the role and the specific characteristics of CI in this rare form of neoplasm, and therefore, more studies are needed in this setting. Full article

(This article belongs to the Special Issue PET/CT and Conventional Imaging in Cancers)

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15 pages, 2341 KiB

Open AccessArticle

Burden of Illness in Follicular Lymphoma with Multiple Lines of Treatment, Italian RWE Analysis

by Andrés J. M. Ferreri, Pier Luigi Zinzani, Carlo Messina, Diletta Valsecchi, Maria Chiara Rendace, Eleonora Premoli, Elisa Giacomini, Chiara Veronesi, Luca Degli Esposti and Paola Di Matteo

Cancers 2023, 15(17), 4403; https://doi.org/10.3390/cancers15174403 - 2 Sep 2023

Cited by 2 | Viewed by 1970

Abstract

This real-world analysis investigated patients with follicular lymphoma in Italy receiving three or more treatment lines (≥3L), focusing on therapeutic pathways with their rebounds on healthcare resource consumptions and costs. Data were retrieved from administrative databases from healthcare entities covering about 13.3 million [...] Read more.

This real-world analysis investigated patients with follicular lymphoma in Italy receiving three or more treatment lines (≥3L), focusing on therapeutic pathways with their rebounds on healthcare resource consumptions and costs. Data were retrieved from administrative databases from healthcare entities covering about 13.3 million residents. Adults diagnosed with follicular lymphoma were identified between January 2015 and June 2020, and among them 2434 patients with ≥3L of treatment during the data availability interval (January 2009 to June 2021) were included. Of them, 1318 were in 3L, 494 in 4L and 622 in ≥5L. A relevant proportion of patients (12–32%) switched to a later line within the same calendar year. At 3-year follow-up (median), 34% patients died. Total mean annual expenses were euro 14,508 in the year preceding inclusion and rose to euro 21,081 at 1-year follow-up (on average euro 22,230/patient/year for the whole follow-up), with hospitalization and drug expenses as weightiest cost items. In conclusion, the clinical and economic burden of follicular lymphoma increases along with later treatment lines. The high mortality rates indicate that further efforts are needed to optimize disease management. Full article

(This article belongs to the Special Issue Advances in Follicular Lymphoma)

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14 pages, 1368 KiB

Open AccessSystematic Review

Methylenetetrahydrofolate Reductase C677T (rs1801133) Polymorphism Is Associated with Bladder Cancer in Asian Population: Epigenetic Meta-Analysis as Precision Medicine Approach

by Athaya Febriantyo Purnomo, Besut Daryanto, Kurnia Penta Seputra, Taufiq Nur Budaya, Nurul Cholifah Lutfiana, Fahrul Nurkolis, Sanghyun Chung, Jin Young Suh, Moon Nyeo Park, Byung-Kwan Seo and Bonglee Kim

Cancers 2023, 15(17), 4402; https://doi.org/10.3390/cancers15174402 - 2 Sep 2023

Cited by 6 | Viewed by 1710

Abstract

The etiology of bladder cancer remains unclear. This study investigates the impact of gene polymorphisms, particularly methylenetetrahydrofolate reductase gene (MTHFR), on bladder cancer susceptibility, focusing on the rs1801133 single-nucleotide polymorphism (SNP). A meta-analysis was conducted after systematically reviewing the MTHFR gene literature, adhering [...] Read more.

The etiology of bladder cancer remains unclear. This study investigates the impact of gene polymorphisms, particularly methylenetetrahydrofolate reductase gene (MTHFR), on bladder cancer susceptibility, focusing on the rs1801133 single-nucleotide polymorphism (SNP). A meta-analysis was conducted after systematically reviewing the MTHFR gene literature, adhering to PRISMA guidelines and registering in PROSPERO (CRD42023423064). Seven studies were included, showing a significant association between the MTHFR C677T (rs1801133) polymorphism and bladder cancer susceptibility. Individuals with the T-allele or TT genotype had a higher likelihood of bladder cancer. In the Asian population, the overall analysis revealed an odds ratio (OR) of 1.15 (95% CI 1.03–1.30; p-value = 0.03) for T-allele versus C-allele and an OR of 1.34 (95% CI 1.04–1.72; p-value = 0.02) for TT genotype versus TC+CC genotype. The CC genotype, however, showed no significant association with bladder cancer. Notably, epigenetic findings displayed low sensitivity but high specificity, indicating reliable identified associations while potentially overlooking some epigenetic factors related to bladder cancer. In conclusion, the MTHFR T-allele and TT genotype were associated with increased bladder cancer risk in the Asian population. These insights into genetic factors influencing bladder cancer susceptibility could inform targeted prevention and treatment strategies. Further research is warranted to validate and expand these findings. Full article

(This article belongs to the Special Issue Advances in Genetics and Epigenetics of Bladder Cancer)

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14 pages, 1321 KiB

Open AccessArticle

Weight Management Effectiveness and Predictors of Dropout in Breast Cancer Survivors: A Retrospective Study

by Edda Cava, Daniele Spadaccini, Gianluca Aimaretti, Paolo Marzullo, Beatrice Cavigiolo, Deborah Farinelli, Alessandra Gennari, Chiara Saggia, Maria Grazia Carbonelli, Sergio Riso and Flavia Prodam

Cancers 2023, 15(17), 4401; https://doi.org/10.3390/cancers15174401 - 2 Sep 2023

Cited by 2 | Viewed by 1447

Abstract

Background: Reducing obesity and weight gain, which often occurs during breast cancer treatment, may represent an efficient secondary or tertiary prevention against cancer. Purpose: This retrospective observational cohort study aimed to assess the impact of a Mediterranean diet on weight and anthropometric changes [...] Read more.

Background: Reducing obesity and weight gain, which often occurs during breast cancer treatment, may represent an efficient secondary or tertiary prevention against cancer. Purpose: This retrospective observational cohort study aimed to assess the impact of a Mediterranean diet on weight and anthropometric changes in women completing active breast cancer treatment. Additionally, we sought to identify factors associated with study dropout within one year. Methods: A total of 182 female patients (20 normal weight, 59 overweight, 103 obese) received personalized Mediterranean diet interventions and underwent monthly outpatient visits. Results: Dropout rates were 42.3% at 6 months and 64.1% at 12 months. Among the obese subgroup, BMI (p < 0.001) and fat mass (p < 0.05) decreased after 6 months. At 12 months, the obese subgroup showed a borderline significant further reduction in BMI (p = 0.062). BMI or weight loss did not predict dropout at any time point. However, age (OR = 0.91) and diastolic blood pressure (OR = 1.07) were significant predictors of dropout at 12 months. Conclusion: Implementing a Mediterranean diet can lead to weight and anthropometric improvements in breast cancer survivors. Further research is necessary to explore the long-term effects of weight loss on these individuals, identify effective dietary approaches, and consider specific predictors of dropout. Full article

(This article belongs to the Special Issue Cancer and Diabetes: What Connections Lie between Them?)

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11 pages, 726 KiB

Open AccessReview

Management of Metastatic Pancreatic Cancer—Comparison of Global Guidelines over the Last 5 Years

by Monika Pajewska, Olga Partyka, Aleksandra Czerw, Andrzej Deptała, Elżbieta Cipora, Izabela Gąska, Marek Wojtaszek, Katarzyna Sygit, Marian Sygit, Edyta Krzych-Fałta, Daria Schneider-Matyka, Anna M. Cybulska, Elżbieta Grochans, Alicja Asendrych-Woźniak, Agnieszka Romanowicz, Jarosław Drobnik, Ewa Bandurska, Weronika Ciećko, Barbara Maciuszek-Bartkowska, Mateusz Curyło, Kacper Wróbel, Remigiusz Kozłowski and Michał Marczak Show full author list Hide full author list

Cancers 2023, 15(17), 4400; https://doi.org/10.3390/cancers15174400 - 2 Sep 2023

Cited by 4 | Viewed by 2476

Abstract

Pancreatic cancer (PC) is usually diagnosed at an advanced stage of its development, which results in lower overall survival (OS). Prognosis is also poor even with curative-intent surgery. Approximately 80% of patients with localized PDAC have micrometastases at the time of diagnosis, which [...] Read more.

Pancreatic cancer (PC) is usually diagnosed at an advanced stage of its development, which results in lower overall survival (OS). Prognosis is also poor even with curative-intent surgery. Approximately 80% of patients with localized PDAC have micrometastases at the time of diagnosis, which leads to a worse prognosis than in other cancers. The objective of this study is to present the progress in the treatment of metastatic pancreatic cancer based on the recommendations of oncological scientific societies, such as ESMO, NCCN, ASCO, NICE and SEOM, over the last 5 years. Combined FOLFIRINOX therapy is mostly a recommended therapy among patients with good performance statuses, while gemcitabine is recommended for more fragile patients as a first-line treatment. The newest guidelines suggest that molecular profiling of the tumor should be the first step in determining the course of treatment. The use of modern molecular therapies in patients with specific gene mutations should extend the survival of patients with this disease. Full article

(This article belongs to the Section Cancer Therapy)

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20 pages, 15475 KiB

Open AccessArticle

Development and Validation of the Oxidative Stress Related lncRNAs for Prognosis in Esophageal Squamous Cell Carcinoma

by Xuan Zheng, Wei Liu, Yingze Zhu, Wenyue Kong, Xin Su, Lanxiang Huang, Yishuang Cui and Guogui Sun

Cancers 2023, 15(17), 4399; https://doi.org/10.3390/cancers15174399 - 2 Sep 2023

Viewed by 1635

Abstract

Esophageal squamous cell cancer (ESCC) is an aggressive disease associated with a poor prognosis. Long non-coding RNAs (lncRNAs) and oxidative stress play crucial roles in tumor progression. We aimed to identify an oxidative stress-related lncRNA signature that could predict the prognosis in ESCC. [...] Read more.

Esophageal squamous cell cancer (ESCC) is an aggressive disease associated with a poor prognosis. Long non-coding RNAs (lncRNAs) and oxidative stress play crucial roles in tumor progression. We aimed to identify an oxidative stress-related lncRNA signature that could predict the prognosis in ESCC. In the GSE53625 dataset, we identified 332 differentially expressed lncRNAs (DElncRNAs) between ESCC and control samples, out of which 174 were oxidative stress-related DElncRNAs. Subsequently, seven oxidative stress-related DElncRNAs (CCR5AS, LINC01749, PCDH9-AS1, TMEM220-AS1, KCNMA1-AS1, SNHG1, LINC01672) were selected based on univariate and LASSO Cox to build a prognostic risk model, and their expression was detected by RT-qPCR. The model exhibited an excellent ability for the prediction of overall survival (OS) and other clinicopathological traits using Kaplan–Meier (K-M) survival curves, receiver operating characteristic (ROC) curves, and the Wilcoxon test. Additionally, analysis of infiltrated immune cells and immune checkpoints indicated differences in immune status between the two risk groups. Finally, the in vitro experiments showed that PCDH9-AS1 overexpression inhibited proliferation ability and promoted apoptosis and oxidative stress levels in ESCC cells. In conclusion, our study demonstrated that a novel oxidative stress-related DElncRNA prognostic model performed favorably in predicting ESCC patient prognosis and benefits personalized clinical applications. Full article

(This article belongs to the Topic Biomarker Development and Application)

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12 pages, 609 KiB

Open AccessArticle

Is Computed-Tomography-Based Body Composition a Reliable Predictor of Chemotherapy-Related Toxicity in Pancreatic Cancer Patients?

by Marco Cefalì, Isabel Scala, Giuliana Pavone, Daniel Helbling, Saskia Hussung, Ralph Fritsch, Cäcilia Reiner, Soleen Stocker, Dieter Koeberle, Marc Kissling, Vito Chianca, Filippo Del Grande, Sara De Dosso and Stefania Rizzo

Cancers 2023, 15(17), 4398; https://doi.org/10.3390/cancers15174398 - 2 Sep 2023

Cited by 1 | Viewed by 1230

Abstract

Background: Malnutrition, loss of weight and of skeletal muscle mass are frequent in pancreatic cancer patients, a majority of which will undergo chemotherapy over the course of their disease. Available data suggest a negative prognostic role of these changes in body composition on [...] Read more.

Background: Malnutrition, loss of weight and of skeletal muscle mass are frequent in pancreatic cancer patients, a majority of which will undergo chemotherapy over the course of their disease. Available data suggest a negative prognostic role of these changes in body composition on disease outcomes; however, it is unclear whether tolerance to chemotherapeutic treatment is similarly and/or negatively affected. We aimed to explore this association by retrospectively assessing changes in body composition and chemotherapy-related toxicity in a cohort of advanced pancreatic cancer patients. Methods: Body composition was evaluated through clinical parameters and through radiological assessment of muscle mass, skeletal muscle area, skeletal muscle index and skeletal muscle density; and an assessment of fat distribution by subcutaneous adipose tissue and visceral adipose tissue. We performed descriptive statistics, pre/post chemotherapy comparisons and uni- and multivariate analyses to assess the relation between changes in body composition and toxicity. Results: Toxicity risk increased with an increase of skeletal muscle index (OR: 1.03) and body mass index (OR: 1.07), whereas it decreased with an increase in skeletal muscle density (OR: 0.96). Multivariate analyses confirmed a reduction in the risk of toxicity only with an increase in skeletal muscle density (OR: 0.96). Conclusions: This study suggests that the retrospective analysis of changes in body composition is unlikely to be useful to predict toxicity to gemcitabine—nab-paclitaxel. Full article

(This article belongs to the Section Cancer Therapy)

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20 pages, 1712 KiB

Open AccessArticle

DCIS and LCIS: Are the Risk Factors for Developing In Situ Breast Cancer Different?

by Jasmine Timbres, Kelly Kohut, Michele Caneppele, Maria Troy, Marjanka K. Schmidt, Rebecca Roylance and Elinor Sawyer

Cancers 2023, 15(17), 4397; https://doi.org/10.3390/cancers15174397 - 2 Sep 2023

Cited by 3 | Viewed by 3059

Abstract

Ductal carcinoma in situ (DCIS) is widely accepted as a precursor of invasive ductal carcinoma (IDC). Lobular carcinoma in situ (LCIS) is considered a risk factor for invasive lobular carcinoma (ILC), and it is unclear whether LCIS is also a precursor. Therefore, it [...] Read more.

Ductal carcinoma in situ (DCIS) is widely accepted as a precursor of invasive ductal carcinoma (IDC). Lobular carcinoma in situ (LCIS) is considered a risk factor for invasive lobular carcinoma (ILC), and it is unclear whether LCIS is also a precursor. Therefore, it would be expected that similar risk factors predispose to both DCIS and IDC, but not necessarily LCIS and ILC. This study examined associations with risk factors using data from 3075 DCIS cases, 338 LCIS cases, and 1584 controls aged 35–60, recruited from the UK-based GLACIER and ICICLE case-control studies between 2007 and 2012. Analysis showed that breastfeeding in parous women was protective against DCIS and LCIS, which is consistent with research on invasive breast cancer (IBC). Additionally, long-term use of HRT in post-menopausal women increased the risk of DCIS and LCIS, with a stronger association in LCIS, similar to the association with ILC. Contrary to findings with IBC, parity and the number of births were not protective against DCIS or LCIS, while oral contraceptives showed an unexpected protective effect. These findings suggest both similarities and differences in risk factors for DCIS and LCIS compared to IBC and that there may be justification for increased breast surveillance in post-menopausal women taking long-term HRT. Full article

(This article belongs to the Section Cancer Therapy)

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22 pages, 997 KiB

Open AccessSystematic Review

Safety and Efficacy of a Single-Stage versus Two-Stage Intramedullary Nailing for Synchronous Impending or Pathologic Fractures of Bilateral Femur for Oncologic Indications: A Systematic Review

by Patrick P. Nian, Vanathi Ganesan, Joydeep Baidya, Ryan S. Marder, Krish Maheshwari, Andriy Kobryn and Aditya V. Maheshwari

Cancers 2023, 15(17), 4396; https://doi.org/10.3390/cancers15174396 - 2 Sep 2023

Viewed by 1213

Abstract

Although intramedullary nail (IMN) fixation is the standard of care for most impending and/or complete pathologic fractures of the femur, the optimal timing/sequence of the IMN in cases of synchronous bilateral femoral disease in advanced cancer is not well established. Thus, we compared [...] Read more.

Although intramedullary nail (IMN) fixation is the standard of care for most impending and/or complete pathologic fractures of the femur, the optimal timing/sequence of the IMN in cases of synchronous bilateral femoral disease in advanced cancer is not well established. Thus, we compared the outcomes of single-stage (SS) vs. two-stage (TS) IMN of the bilateral femur with a systematic review of the literature on this topic. Bilateral SS and TS IMN cases were identified from 14 studies extracted from four databases according to PRISMA guidelines. Safety (complications, reoperations, mortality, survival, blood loss, and transfusion) and efficacy (length of stay [LOS], time to start rehabilitation and adjuvant therapy, functional scores, and cost) were compared between the groups. A total of 156 IMNs in 78 patients (36 SS and 42 TS) were analyzed. There were one surgical (infection in TS requiring reoperation; p = 0.860) and fifteen medical complications (five in SS, ten in TS; p = 0.045), with SS being associated with lower rates of total and medical complications. Survival, intraoperative mortality, and postoperative same-admission mortality were similar. No cases of implant failure were reported. Data on LOS, rehabilitation, and adjuvant therapy were scarcely reported, although one study favored SS over TS. No study compared cost or functional scores. Our study is the largest and most comprehensive of its kind in supporting the safety and efficacy of a SS bilateral femur IMN approach in these select patients. Further investigations with higher levels of evidence are warranted to optimize treatment protocols for this clinical scenario. Full article

(This article belongs to the Special Issue Sarcoma and Bone Cancer Awareness Month)

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17 pages, 3895 KiB

Open AccessEditor’s ChoiceArticle

Unlocking the Power of Benchmarking: Real-World-Time Data Analysis for Enhanced Sarcoma Patient Outcomes

by Bruno Fuchs, Georg Schelling, Maria Elyes, Gabriela Studer, Beata Bode-Lesniewska, Mario F. Scaglioni, Pietro Giovanoli, Philip Heesen and on behalf of the SwissSarcomaNetwork

Cancers 2023, 15(17), 4395; https://doi.org/10.3390/cancers15174395 - 2 Sep 2023

Cited by 11 | Viewed by 2506

Abstract

Benchmarking is crucial for healthcare providers to enhance quality and efficiency, notably for complex conditions like sarcomas. Multidisciplinary teams/sarcoma boards (MDT/SBs) are vital in sarcoma management, but differences in their processes can affect patient outcomes and treatment costs, despite adherence to international guidelines. [...] Read more.

Benchmarking is crucial for healthcare providers to enhance quality and efficiency, notably for complex conditions like sarcomas. Multidisciplinary teams/sarcoma boards (MDT/SBs) are vital in sarcoma management, but differences in their processes can affect patient outcomes and treatment costs, despite adherence to international guidelines. To address this issue, this study aimed to compare two MDT/SBs and establish an interoperable digital platform, Sarconnector^®, for real-time-world data assessment and automated analysis. The study included 983 patients, 46.0% of whom female, with a median age of 58 years, and 4.5% of patients presented with metastasis at diagnosis. Differences were observed in the number of first-time presentations, follow-up presentations, primary sarcomas, biopsies and chemotherapy indications between the two MDT/SB. The results highlight the importance of benchmarking and utilizing a harmonized data approach, such as the RWT approach provided by the Sarconnector^®, to standardize and evaluate quality and cost metrics. By identifying areas of improvement and making data-driven decisions on the meta-level, healthcare providers can optimize resources and improve patient outcomes. In conclusion, benchmarking with the RWT harmonized data approach provided by the Sarconnector^® can help healthcare providers improve the overall effectiveness of the healthcare system and achieve better outcomes for their patients in terms of both outcomes and costs. Full article

(This article belongs to the Special Issue Global Management of Sarcoma Data: Is Real-Time Predictive Analytics on the Horizon?)

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16 pages, 1451 KiB

Open AccessArticle

Expanding the Clinical Utility of Targeted RNA Sequencing Panels beyond Gene Fusions to Complex, Intragenic Structural Rearrangements

by Kathleen M. Schieffer, Amanda Moccia, Brianna A. Bucknor, Eileen Stonerock, Vijayakumar Jayaraman, Heather Jenkins, Aimee McKinney, Selene C. Koo, Mariam T. Mathew, Elaine R. Mardis, Kristy Lee, Shalini C. Reshmi and Catherine E. Cottrell

Cancers 2023, 15(17), 4394; https://doi.org/10.3390/cancers15174394 - 2 Sep 2023

Viewed by 1448

Abstract

Gene fusions are a form of structural rearrangement well established as driver events in pediatric and adult cancers. The identification of such events holds clinical significance in the refinement, prognostication, and provision of treatment in cancer. Structural rearrangements also extend beyond fusions to [...] Read more.

Gene fusions are a form of structural rearrangement well established as driver events in pediatric and adult cancers. The identification of such events holds clinical significance in the refinement, prognostication, and provision of treatment in cancer. Structural rearrangements also extend beyond fusions to include intragenic rearrangements, such as internal tandem duplications (ITDs) or exon-level deletions. These intragenic events have been increasingly implicated as cancer-promoting events. However, the detection of intragenic rearrangements may be challenging to resolve bioinformatically with short-read sequencing technologies and therefore may not be routinely assessed in panel-based testing. Within an academic clinical laboratory, over three years, a total of 608 disease-involved samples (522 hematologic malignancy, 86 solid tumors) underwent clinical testing using Anchored Multiplex PCR (AMP)-based RNA sequencing. Hematologic malignancies were evaluated using a custom Pan-Heme 154 gene panel, while solid tumors were assessed using a custom Pan-Solid 115 gene panel. Gene fusions, ITDs, and intragenic deletions were assessed for diagnostic, prognostic, or therapeutic significance. When considering gene fusions alone, we report an overall diagnostic yield of 36% (37% hematologic malignancy, 41% solid tumors). When including intragenic structural rearrangements, the overall diagnostic yield increased to 48% (48% hematologic malignancy, 45% solid tumor). We demonstrate the clinical utility of reporting structural rearrangements, including gene fusions and intragenic structural rearrangements, using an AMP-based RNA sequencing panel. Full article

(This article belongs to the Topic Advances in Genetics and Precision Medicine in Human Diseases)

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Cancers, Volume 15, Issue 17 (September-1 2023) – 225 articles

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