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      Prognostic value of COL10A1 and its correlation with tumor-infiltrating immune cells in urothelial bladder cancer: A comprehensive study based on bioinformatics and clinical analysis validation

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          Abstract

          Introduction

          Bladder cancer (BLCA) is one of the most lethal diseases. COL10A1 is secreted small-chain collagen in the extracellular matrix associated with various tumors, including gastric, colon, breast, and lung cancer. However, the role of COL10A1 in BLCA remains unclear. This is the first research focusing on the prognostic value of COL10A1 in BLCA. In this research, we aimed to uncover the association between COL10A1 and the prognosis, as well as other clinicopathological parameters in BLCA.

          Methods

          We obtained gene expression profiles of BLCA and normal tissues from the TCGA, GEO, and ArrayExpress databases. Immunohistochemistry staining was performed to investigate the protein expression and prognostic value of COL10A1 in BLCA patients. GO and KEGG enrichment along with GSEA analyses were performed to reveal the biological functions and potential regulatory mechanisms of COL10A1 based on the gene co-expression network. We used the “maftools” R package to display the mutation profiles between the high and low COL10A1 groups. GIPIA2, TIMER, and CIBERSORT algorithms were utilized to explore the effect of COL10A1 on the tumor immune microenvironment.

          Results

          We found that COL10A1 was upregulated in the BLCA samples, and increased COL10A1 expression was related to poor overall survival. Functional annotation of 200 co-expressed genes positively correlated with COL10A1 expression, including GO, KEGG, and GSEA enrichment analyses, indicated that COL10A1 was basically involved in the extracellular matrix, protein modification, molecular binding, ECM-receptor interaction, protein digestion and absorption, focal adhesion, and PI3K-Akt signaling pathway. The most commonly mutated genes of BLCA were different between high and low COL10A1 groups. Tumor immune infiltrating analyses showed that COL10A1 might have an essential role in recruiting infiltrating immune cells and regulating immunity in BLCA, thus affecting prognosis. Finally, external datasets and biospecimens were used, and the results further validated the aberrant expression of COL10A1 in BLCA samples.

          Conclusions

          In conclusion, our study demonstrates that COL10A1 is an underlying prognostic and predictive biomarker in BLCA.

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          Most cited references81

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles

            Although genomewide RNA expression analysis has become a routine tool in biomedical research, extracting biological insight from such information remains a major challenge. Here, we describe a powerful analytical method called Gene Set Enrichment Analysis (GSEA) for interpreting gene expression data. The method derives its power by focusing on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation. We demonstrate how GSEA yields insights into several cancer-related data sets, including leukemia and lung cancer. Notably, where single-gene analysis finds little similarity between two independent studies of patient survival in lung cancer, GSEA reveals many biological pathways in common. The GSEA method is embodied in a freely available software package, together with an initial database of 1,325 biologically defined gene sets.
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              Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources.

              DAVID bioinformatics resources consists of an integrated biological knowledgebase and analytic tools aimed at systematically extracting biological meaning from large gene/protein lists. This protocol explains how to use DAVID, a high-throughput and integrated data-mining environment, to analyze gene lists derived from high-throughput genomic experiments. The procedure first requires uploading a gene list containing any number of common gene identifiers followed by analysis using one or more text and pathway-mining tools such as gene functional classification, functional annotation chart or clustering and functional annotation table. By following this protocol, investigators are able to gain an in-depth understanding of the biological themes in lists of genes that are enriched in genome-scale studies.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                17 March 2023
                2023
                : 14
                : 955949
                Affiliations
                [1] Department of Urology/Institute of Urology, West China Hospital, Sichuan University , Chengdu, Sichuan, China
                Author notes

                Edited by: Roi Gazit, Ben Gurion University of the Negev, Israel

                Reviewed by: Zhaohui Chen, Huazhong University of Science and Technology, China; Hamid Morjani, Université de Reims Champagne-Ardenne, France; Wei-Jan Wang, China Medical University, Taiwan; Felice Crocetto, Federico II University Hospital, Italy

                *Correspondence: Ping Han, hanping@ 123456scu.edu.cn

                †These authors have contributed equally to this work

                This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2023.955949
                10063846
                37006317
                8ed887cb-c643-46fa-b347-52f711af5333
                Copyright © 2023 Wang, Bai, Zhang, Li, Chen, Wu, Tang, Wei and Han

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 29 May 2022
                : 22 February 2023
                Page count
                Figures: 8, Tables: 2, Equations: 0, References: 81, Pages: 17, Words: 7139
                Funding
                This study was supported by the National Key Research and Development Program of China (2021YFC2009303), Project of Health Commission of Sichuan Province (21PJ041) and the Key Research and Development Support Plan of Chengdu Science and Technology Bureau (2022-YF05-01568-SN).
                Categories
                Immunology
                Original Research

                Immunology
                col10a1,urothelial bladder cancer,prognosis,bioinformatics,tumor microenvironment,tumor-infiltrating immune cell

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