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Cancer Biomarkers and Bioinformatics

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 16862

Special Issue Editors

Department of Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawaii, 651 Ilalo Street, Honolulu, HI 96813, USA
Interests: bioinformatics; genomics; biomarker; systems biology; biomedical informatics; cancer
Special Issues, Collections and Topics in MDPI journals
Center for Epigenetics & Disease Prevention, Institute of Biosciences & Technology, College of Medicine, Texas A&M University, Houston, TX, USA
Interests: maternal nutrition; environmental health; development; bioinformatics; epigenetics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer biomarkers include any measurable molecular indicators of cancer risk, cancer occurrence, or patient outcome, and can be used as tools for cancer risk assessment, screening and early detection; accurate diagnosis; patient prognosis; prediction of response to therapy; and cancer surveillance and monitoring response. They can also be developed as targeted therapies. Cancer biomarkers can be measured in tissue and liquid biopsy. Due to the development of advanced technologies such as omics and nanotechnologies, a huge amount of data related to cancer biomarkers have been generated. Bioinformatics plays a key role in correctly generating firsthand data, and in leveraging secondary cancer biomarker data. Bioinformatics is involved in the biomarker discovery process, bridging the gap between initial discovery phases such as experimental design, clinical study execution, and bioanalytics, including sample preparation, separation and high-throughput profiling, as well as data integration and the independent validation of identified candidates.

This Special Issue welcomes all kinds of submissions which include the use of bioinformatics to process experimentally generated and/or published datasets for cancer biomarker studies.

This special issue is supervised by Prof. Dr. Youping Deng, Dr. Kurt K. Zhang and assisted by Dr. Yuanyuan Fu.

Prof. Dr. Youping Deng
Dr. Kurt K. Zhang
Guest Editors

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Published Papers (11 papers)

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Research

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18 pages, 2176 KiB  
Article
5′-Isoforms of miR-1246 Have Distinct Targets and Stronger Functional Impact Compared with Canonical miR-1246 in Colorectal Cancer Cells In Vitro
by Rokas Lukosevicius, Gediminas Alzbutas, Greta Varkalaite, Violeta Salteniene, Deimante Tilinde, Simonas Juzenas, Ugne Kulokiene, Dainius Janciauskas, Lina Poskiene, Kestutis Adamonis, Gediminas Kiudelis, Juozas Kupcinskas and Jurgita Skieceviciene
Int. J. Mol. Sci. 2024, 25(5), 2808; https://doi.org/10.3390/ijms25052808 - 28 Feb 2024
Viewed by 447
Abstract
Colorectal cancer (CRC) is a multifactorial disease involving genetic and epigenetic factors, such as miRNAs. Sequencing-based studies have revealed that miRNAs have many isoforms (isomiRs) with modifications at the 3′- and 5′-ends or in the middle, resulting in distinct targetomes and, consequently, functions. [...] Read more.
Colorectal cancer (CRC) is a multifactorial disease involving genetic and epigenetic factors, such as miRNAs. Sequencing-based studies have revealed that miRNAs have many isoforms (isomiRs) with modifications at the 3′- and 5′-ends or in the middle, resulting in distinct targetomes and, consequently, functions. In the present study, we aimed to evaluate the putative targets and functional role of miR-1246 and its two 5′-isoforms (ISO-miR-1246_a and ISO-miR-1246_G) in vitro. Commercial Caco-2 cells of CRC origin were analyzed for the expression of WT-miR-1246 and its 5′-isoforms using small RNA sequencing data, and the overabundance of the two miR-1246 isoforms was determined in cells. The transcriptome analysis of Caco-2 cells transfected with WT-miR-1246, ISO-miR-1246_G, and ISO-miR-1246_a indicated the minor overlap of the targetomes between the studied miRNA isoforms. Consequently, an enrichment analysis showed the involvement of the potential targets of the miR-1246 isoforms in distinct signaling pathways. Cancer-related pathways were predominantly more enriched in dysregulated genes in ISO-miR-1246_G and ISO-miR-1246_a, whereas cell cycle pathways were more enriched in WT-miR-1246. The functional analysis of WT-miR-1246 and its two 5′-isoforms revealed that the inhibition of any of these molecules had a tumor-suppressive role (reduced cell viability and migration and promotion of early cell apoptosis) in CRC cells. However, the 5′-isoforms had a stronger effect on viability compared with WT-miR-1246. To conclude, this research shows that WT-miR-1246 and its two 5′-isoforms have different targetomes and are involved in distinct signaling pathways but collectively play an important role in CRC pathogenesis. Full article
(This article belongs to the Special Issue Cancer Biomarkers and Bioinformatics)
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16 pages, 3787 KiB  
Article
Exploring Optimal Biomarker Sources: A Comparative Analysis of Exosomes and Whole Plasma in Fasting and Non-Fasting Conditions for Liquid Biopsy Applications
by Masaki Nasu, Vedbar S. Khadka, Mayumi Jijiwa, Ken Kobayashi and Youping Deng
Int. J. Mol. Sci. 2024, 25(1), 371; https://doi.org/10.3390/ijms25010371 - 27 Dec 2023
Viewed by 647
Abstract
The study of liquid biopsy with plasma samples is being conducted to identify biomarkers for clinical use. Exosomes, containing nucleic acids and metabolites, have emerged as possible sources for biomarkers. To evaluate the effectiveness of exosomes over plasma, we analyzed the small non-coding [...] Read more.
The study of liquid biopsy with plasma samples is being conducted to identify biomarkers for clinical use. Exosomes, containing nucleic acids and metabolites, have emerged as possible sources for biomarkers. To evaluate the effectiveness of exosomes over plasma, we analyzed the small non-coding RNAs (sncRNAs) and metabolites extracted from exosomes in comparison to those directly extracted from whole plasma under both fasting and non-fasting conditions. We found that sncRNA profiles were not affected by fasting in either exosome or plasma samples. Our results showed that exosomal sncRNAs were found to have more consistent profiles. The plasma miRNA profiles contained high concentrations of cell-derived miRNAs that were likely due to hemolysis. We determined that certain metabolites in whole plasma exhibited noteworthy concentration shifts in relation to fasting status, while others did not. Here, we propose that (1) fasting is not required for a liquid biopsy study that involves both sncRNA and metabolomic profiling, as long as metabolites that are not influenced by fasting status are selected, and (2) the utilization of exosomal RNAs promotes robust and consistent findings in plasma samples, mitigating the impact of batch effects derived from hemolysis. These findings advance the optimization of liquid biopsy methodologies for clinical applications. Full article
(This article belongs to the Special Issue Cancer Biomarkers and Bioinformatics)
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19 pages, 6755 KiB  
Article
Systematic Multiomic Analysis of PKHD1L1 Gene Expression and Its Role as a Predicting Biomarker for Immune Cell Infiltration in Skin Cutaneous Melanoma and Lung Adenocarcinoma
by Ji Young Kang, Jisun Yang, Haeryung Lee, Soochul Park, Minchan Gil and Kyung Eun Kim
Int. J. Mol. Sci. 2024, 25(1), 359; https://doi.org/10.3390/ijms25010359 - 26 Dec 2023
Viewed by 848
Abstract
The identification of genetic factors that regulate the cancer immune microenvironment is important for understanding the mechanism of tumor progression and establishing an effective treatment strategy. Polycystic kidney and hepatic disease 1-like protein 1 (PKHD1L1) is a large transmembrane protein that is highly [...] Read more.
The identification of genetic factors that regulate the cancer immune microenvironment is important for understanding the mechanism of tumor progression and establishing an effective treatment strategy. Polycystic kidney and hepatic disease 1-like protein 1 (PKHD1L1) is a large transmembrane protein that is highly expressed in immune cells; however, its association with tumor progression remains unclear. Here, we systematically analyzed the clinical relevance of PKHD1L1 in the tumor microenvironment in multiple cancer types using various bioinformatic tools. We found that the PKHD1L1 mRNA expression levels were significantly lower in skin cutaneous melanoma (SKCM) and lung adenocarcinoma (LUAD) than in normal tissues. The decreased expression of PKHD1L1 was significantly associated with unfavorable overall survival (OS) in SKCM and LUAD. Additionally, PKHD1L1 expression was positively correlated with the levels of infiltrating B cells, cluster of differentiation (CD)-8+ T cells, and natural killer (NK) cells, suggesting that the infiltration of immune cells could be associated with a good prognosis due to increased PKHD1L1 expression. Gene ontology (GO) analysis also revealed the relationship between PKHD1L1-co-altered genes and the activation of lymphocytes, including B and T cells. Collectively, this study shows that PKHD1L1 expression is positively correlated with a good prognosis via the induction of immune infiltration, suggesting that PKHD1L1 has potential prognostic value in SKCM and LUAD. Full article
(This article belongs to the Special Issue Cancer Biomarkers and Bioinformatics)
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19 pages, 5395 KiB  
Article
Identification of NCAPG as an Essential Gene for Neuroblastoma Employing CRISPR-Cas9 Screening Database and Experimental Verification
by Yubin Jia, Jiaxing Yang, Yankun Chen, Yun Liu, Yan Jin, Chaoyu Wang, Baocheng Gong and Qiang Zhao
Int. J. Mol. Sci. 2023, 24(19), 14946; https://doi.org/10.3390/ijms241914946 - 06 Oct 2023
Viewed by 1061
Abstract
Neuroblastoma is the most common extracranial solid tumor in children. Patients with neuroblastoma have a poor prognosis. The development of therapy targets and the ability to predict prognosis will be enhanced through further exploration of the genetically related genes of neuroblastoma. The present [...] Read more.
Neuroblastoma is the most common extracranial solid tumor in children. Patients with neuroblastoma have a poor prognosis. The development of therapy targets and the ability to predict prognosis will be enhanced through further exploration of the genetically related genes of neuroblastoma. The present investigation utilized CRISPR-Cas9 genome-wide screening based on the DepMap database to determine essential genes for neuroblastoma cells’ continued survival. WGCNA analysis was used to determine the progression-related genes, and a prognostic signature was constructed. The signature gene, NCAPG, was downregulated in neuroblastoma cells to explore its impact on various cellular processes. This research used DepMap and WGCNA to pinpoint 45 progression-related essential genes for neuroblastoma. A risk signature comprising NCAPG and MAD2L1 was established. The suppression of NCAPG prevented neuroblastoma cells from proliferating, migrating, and invading. The results of flow cytometric analysis demonstrated that NCAPG inhibition caused cell cycle arrest during the G2 and S phases and the activation of apoptosis. Additionally, NCAPG downregulation activated the p53-mediated apoptotic pathway, inducing cell apoptosis. The present work showed that NCAPG knockdown reduced neuroblastoma cell progression and may serve as a basis for further investigation into diagnostic indicators and therapy targets for neuroblastoma. Full article
(This article belongs to the Special Issue Cancer Biomarkers and Bioinformatics)
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19 pages, 6000 KiB  
Article
Serpin Family A Member 1 Is Prognostic and Involved in Immunological Regulation in Human Cancers
by Xingwang Kuai, Jiaying Lv, Junyu Zhang, Manyu Xu and Juling Ji
Int. J. Mol. Sci. 2023, 24(14), 11566; https://doi.org/10.3390/ijms241411566 - 17 Jul 2023
Viewed by 1352
Abstract
Serpin family A member 1 (SERPINA1) encodes a protease inhibitor participating in many human diseases, but its value in immunoregulation and prognosis of human cancers remains unclear. In this study, through comprehensive analysis of data from The Cancer Genome Atlas (TCGA) datasets, we [...] Read more.
Serpin family A member 1 (SERPINA1) encodes a protease inhibitor participating in many human diseases, but its value in immunoregulation and prognosis of human cancers remains unclear. In this study, through comprehensive analysis of data from The Cancer Genome Atlas (TCGA) datasets, we found that SERPINA1 was dysregulated in many cancers compared with normal tissues. SERPINA1 expression was significantly associated with prognosis, immune subtype, molecular subtype, immune checkpoint (ICP) genes, tumor mutational burden (TMB), microsatellite instability (MSI), and the estimation of stromal and immune cells in malignant tumor tissues using expression data (ESTIMATE) score. There was a strong connection between SERPINA1 expression and tumor-infiltrating lymphocytes, and SERPINA1 showed significant relation to gene markers of immune cells in digestive tumors. Fluorescence-based multiplex immunohistochemistry confirmed that SERPINA1 protein expression was related to clinicopathologic features and immune infiltrates in hepatic cancer. This study suggests that SERPINA can potentially serve as a novel biomarker for cancer prognosis and immunotherapy. Full article
(This article belongs to the Special Issue Cancer Biomarkers and Bioinformatics)
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18 pages, 6443 KiB  
Article
Network Analysis of Biomarkers Associated with Occupational Exposure to Benzene and Malathion
by Marcus Vinicius C. Santos, Arthur S. Feltrin, Isabele C. Costa-Amaral, Liliane R. Teixeira, Jamila A. Perini, David C. Martins, Jr. and Ariane L. Larentis
Int. J. Mol. Sci. 2023, 24(11), 9415; https://doi.org/10.3390/ijms24119415 - 28 May 2023
Viewed by 2151
Abstract
Complex diseases are associated with the effects of multiple genes, proteins, and biological pathways. In this context, the tools of Network Medicine are compatible as a platform to systematically explore not only the molecular complexity of a specific disease but may also lead [...] Read more.
Complex diseases are associated with the effects of multiple genes, proteins, and biological pathways. In this context, the tools of Network Medicine are compatible as a platform to systematically explore not only the molecular complexity of a specific disease but may also lead to the identification of disease modules and pathways. Such an approach enables us to gain a better understanding of how environmental chemical exposures affect the function of human cells, providing better perceptions about the mechanisms involved and helping to monitor/prevent exposure and disease to chemicals such as benzene and malathion. We selected differentially expressed genes for exposure to benzene and malathion. The construction of interaction networks was carried out using GeneMANIA and STRING. Topological properties were calculated using MCODE, BiNGO, and CentiScaPe, and a Benzene network composed of 114 genes and 2415 interactions was obtained. After topological analysis, five networks were identified. In these subnets, the most interconnected nodes were identified as: IL-8, KLF6, KLF4, JUN, SERTAD1, and MT1H. In the Malathion network, composed of 67 proteins and 134 interactions, HRAS and STAT3 were the most interconnected nodes. Path analysis, combined with various types of high-throughput data, reflects biological processes more clearly and comprehensively than analyses involving the evaluation of individual genes. We emphasize the central roles played by several important hub genes obtained by exposure to benzene and malathion. Full article
(This article belongs to the Special Issue Cancer Biomarkers and Bioinformatics)
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28 pages, 5514 KiB  
Article
Next Generation of Ovarian Cancer Detection Using Aptamers
by Rayane da Silva Abreu, Deborah Antunes, Aline dos Santos Moreira, Fabio Passetti, Julia Badaró Mendonça, Natássia Silva de Araújo, Tayanne Felippe Sassaro, Anael Viana Pinto Alberto, Nina Carrossini, Priscila Valverde Fernandes, Mayla Abrahim Costa, Ana Carolina Ramos Guimarães, Wim Maurits Sylvain Degrave and Mariana Caldas Waghabi
Int. J. Mol. Sci. 2023, 24(7), 6315; https://doi.org/10.3390/ijms24076315 - 28 Mar 2023
Cited by 4 | Viewed by 1814
Abstract
Ovarian cancer is among the seven most common types of cancer in women, being the most fatal gynecological tumor, due to the difficulty of detection in early stages. Aptamers are important tools to improve tumor diagnosis through the recognition of specific molecules produced [...] Read more.
Ovarian cancer is among the seven most common types of cancer in women, being the most fatal gynecological tumor, due to the difficulty of detection in early stages. Aptamers are important tools to improve tumor diagnosis through the recognition of specific molecules produced by tumors. Here, aptamers and their potential targets in ovarian cancer cells were analyzed by in silico approaches. Specific aptamers were selected by the Cell-SELEX method using Caov-3 and OvCar-3 cells. The five most frequent aptamers obtained from the last round of selection were computationally modeled. The potential targets for those aptamers in cells were proposed by analyzing proteomic data available for the Caov-3 and OvCar-3 cell lines. Overexpressed proteins for each cell were characterized as to their three-dimensional model, cell location, and electrostatic potential. As a result, four specific aptamers for ovarian tumors were selected: AptaC2, AptaC4, AptaO1, and AptaO2. Potential targets were identified for each aptamer through Molecular Docking, and the best complexes were AptaC2-FXYD3, AptaC4-ALPP, AptaO1-TSPAN15, and AptaO2-TSPAN15. In addition, AptaC2 and AptaO1 could detect different stages and subtypes of ovarian cancer tissue samples. The application of this technology makes it possible to propose new molecular biomarkers for the differential diagnosis of epithelial ovarian cancer. Full article
(This article belongs to the Special Issue Cancer Biomarkers and Bioinformatics)
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14 pages, 8525 KiB  
Article
Identification and Biological Validation of a Chemokine/Chemokine Receptor-Based Risk Model for Predicting Immunotherapeutic Response and Prognosis in Head and Neck Squamous Cell Carcinoma
by Ye Wang, Shimeng Wang, Houshang Wang, Jin Yang and Hongmei Zhou
Int. J. Mol. Sci. 2023, 24(4), 3317; https://doi.org/10.3390/ijms24043317 - 07 Feb 2023
Viewed by 1419
Abstract
Over 80% of head and neck squamous cell carcinoma (HNSCC) patients failed to respond to immunotherapy, which can likely be attributed to the tumor microenvironment (TME) remolding mediated by chemokines/chemokine receptors (C/CR). This study aimed to establish a C/CR-based risk model for better [...] Read more.
Over 80% of head and neck squamous cell carcinoma (HNSCC) patients failed to respond to immunotherapy, which can likely be attributed to the tumor microenvironment (TME) remolding mediated by chemokines/chemokine receptors (C/CR). This study aimed to establish a C/CR-based risk model for better immunotherapeutic responses and prognosis. After assessing the characteristic patterns of the C/CR cluster from the TCGA-HNSCC cohort, a six-gene C/CR-based risk model was developed to stratify patients by LASSO Cox analysis. The screened genes were multidimensionally validated by RT-qPCR, scRNA-seq, and protein data. A total of 30.4% of patients in the low-risk group had better responses to anti-PD-L1 immunotherapy. A Kaplan–Meier analysis showed that patients in the low-risk group had longer overall survival. A time-dependent receiver operating characteristic curve and Cox analyses indicated that risk score served as an independent predictive indicator. The robustness of the immunotherapy response and prognosis prediction was also validated in independent external datasets. Additionally, the TME landscape revealed that the low-risk group was immune activated. Furthermore, the cell communication analysis on the scRNA-seq dataset revealed that cancer-associated fibroblasts were the main communicators within the C/CR ligand–receptor network of TME. Collectively, The C/CR-based risk model simultaneously predicted immunotherapeutic response and prognosis, potentially optimizing personalized therapeutic strategies of HNSCC. Full article
(This article belongs to the Special Issue Cancer Biomarkers and Bioinformatics)
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21 pages, 14593 KiB  
Article
Integrated Analysis of Bulk RNA-Seq and Single-Cell RNA-Seq Unravels the Influences of SARS-CoV-2 Infections to Cancer Patients
by Yu Chen, Yujia Qin, Yuanyuan Fu, Zitong Gao and Youping Deng
Int. J. Mol. Sci. 2022, 23(24), 15698; https://doi.org/10.3390/ijms232415698 - 10 Dec 2022
Cited by 1 | Viewed by 2316
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious and pathogenic coronavirus that emerged in late 2019 and caused a pandemic of respiratory illness termed as coronavirus disease 2019 (COVID-19). Cancer patients are more susceptible to SARS-CoV-2 infection. The treatment of [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious and pathogenic coronavirus that emerged in late 2019 and caused a pandemic of respiratory illness termed as coronavirus disease 2019 (COVID-19). Cancer patients are more susceptible to SARS-CoV-2 infection. The treatment of cancer patients infected with SARS-CoV-2 is more complicated, and the patients are at risk of poor prognosis compared to other populations. Patients infected with SARS-CoV-2 are prone to rapid development of acute respiratory distress syndrome (ARDS) of which pulmonary fibrosis (PF) is considered a sequelae. Both ARDS and PF are factors that contribute to poor prognosis in COVID-19 patients. However, the molecular mechanisms among COVID-19, ARDS and PF in COVID-19 patients with cancer are not well-understood. In this study, the common differentially expressed genes (DEGs) between COVID-19 patients with and without cancer were identified. Based on the common DEGs, a series of analyses were performed, including Gene Ontology (GO) and pathway analysis, protein–protein interaction (PPI) network construction and hub gene extraction, transcription factor (TF)–DEG regulatory network construction, TF–DEG–miRNA coregulatory network construction and drug molecule identification. The candidate drug molecules (e.g., Tamibarotene CTD 00002527) obtained by this study might be helpful for effective therapeutic targets in COVID-19 patients with cancer. In addition, the common DEGs among ARDS, PF and COVID-19 patients with and without cancer are TNFSF10 and IFITM2. These two genes may serve as potential therapeutic targets in the treatment of COVID-19 patients with cancer. Changes in the expression levels of TNFSF10 and IFITM2 in CD14+/CD16+ monocytes may affect the immune response of COVID-19 patients. Specifically, changes in the expression level of TNFSF10 in monocytes can be considered as an immune signature in COVID-19 patients with hematologic cancer. Targeting N6-methyladenosine (m6A) pathways (e.g., METTL3/SERPINA1 axis) to restrict SARS-CoV-2 reproduction has therapeutic potential for COVID-19 patients. Full article
(This article belongs to the Special Issue Cancer Biomarkers and Bioinformatics)
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16 pages, 3871 KiB  
Article
Prognostic and Immunological Role of STK38 across Cancers: Friend or Foe?
by Yankuo Liu, Zhiyuan Shi, Zeyuan Zheng, Jinxin Li, Kunao Yang, Chunlan Xu, Qing Liu, Zhicheng Gong, Yi Yang, Yue Zhao, Zuodong Xuan, Huimin Sun and Chen Shao
Int. J. Mol. Sci. 2022, 23(19), 11590; https://doi.org/10.3390/ijms231911590 - 30 Sep 2022
Cited by 4 | Viewed by 1715
Abstract
Although STK38 (serine-threonine kinase 38) has been proven to play an important role in cancer initiation and progression based on a series of cell and animal experiments, no systemic assessment of STK38 across human cancers is available. We firstly performed a pan-cancer analysis [...] Read more.
Although STK38 (serine-threonine kinase 38) has been proven to play an important role in cancer initiation and progression based on a series of cell and animal experiments, no systemic assessment of STK38 across human cancers is available. We firstly performed a pan-cancer analysis of STK38 in this study. The expression level of STK38 was significantly different between tumor and normal tissues in 15 types of cancers. Meanwhile, a prognosis analysis showed that a distinct relationship existed between STK38 expression and the clinical prognosis of cancer patients. Furthermore, the expression of STK38 was related to the infiltration of immune cells, such as NK cells, memory CD4+ T cells, mast cells and cancer-associated fibroblasts in a few cancers. There were three immune-associated signaling pathways involved in KEGG analysis of STK38. In general, STK38 shows a significant prognostic value in different cancers and is closely associated with cancer immunity. Full article
(This article belongs to the Special Issue Cancer Biomarkers and Bioinformatics)
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Review

Jump to: Research

12 pages, 1835 KiB  
Review
Unveiling the Prognostic Significance of BCL6+/CD10+ Mantle Cell Lymphoma: Meta-Analysis of Individual Patients and Systematic Review
by Dani Ran Castillo, Daniel Park, Won Jin Jeon, Bowon Joung, Jae Lee, Chieh Yang, Bryan Pham, Christopher Hino, Esther Chong, Andrea Shields, Anthony Nguyen, Joel Brothers, Yan Liu, Ke K. Zhang and Huynh Cao
Int. J. Mol. Sci. 2023, 24(12), 10207; https://doi.org/10.3390/ijms241210207 - 16 Jun 2023
Viewed by 1368
Abstract
Mantle cell lymphoma (MCL) is a type of non-Hodgkin lymphoma (NHL) characterized by a hallmark translocation of t (11; 14). CD10 negativity has been used to differentiate MCL from other NHL types; however, recently, there has been an increase in the number of [...] Read more.
Mantle cell lymphoma (MCL) is a type of non-Hodgkin lymphoma (NHL) characterized by a hallmark translocation of t (11; 14). CD10 negativity has been used to differentiate MCL from other NHL types; however, recently, there has been an increase in the number of reported cases of CD10-positive MCL. This warrants further investigation into this rarer immunophenotype and its clinical significance. BCL6, which is a master transcription factor for the regulation of cell proliferation and key oncogene in B cell lymphomagenesis, has been reported to have co-expression with CD10 in MCL. The clinical significance of this aberrant antigen expression remains unknown. We conducted a systematic review by searching four databases and selected five retrospective analyses and five case series. Two survival analyses were conducted to determine if BCL6 positivity conferred a survival difference: 1. BCL6+ vs. BCL6− MCL. 2. BCL6+/CD10+ vs. BCL6−/CD10+ MCL. Correlation analysis was conducted to determine if BCL6 positivity correlated with the Ki67 proliferation index (PI). Overall survival (OS) rates were performed by the Kaplan–Meier method and log-rank test. Our analyses revealed that BCL6+ MCL had significantly shorter overall survival (median OS: 14 months vs. 43 months; p = 0.01), BCL6+/CD10+ MCL had an inferior outcome vs. BCL6+/CD10− MCL (median OS: 20 months vs. 55 months p = 0.1828), BCL6+ MCL had significantly higher percentages of Ki67% (Ki67% difference: 24.29; p = 0.0094), and BCL6 positivity had a positive correlation with CD10+ status with an odds ratio 5.11 (2.49, 10.46; p = 0.0000286). Our analysis showed that BCL6 expression is correlated with CD10 positivity in MCL, and BCL6 expression demonstrated an inferior overall survival. The higher Ki67 PI in BCL6+ MCL compared to BCL6− MCL further supports the idea that the BCL6+ immunophenotype may have prognostic value in MCL. MCL management should consider incorporating prognostic scoring systems adjusted for BCL6 expression. Targeted therapies against BCL6 may offer potential therapeutic options for managing MCL with aberrant immunophenotypes. Full article
(This article belongs to the Special Issue Cancer Biomarkers and Bioinformatics)
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