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      Identification of Therapeutic Targets and Prognostic Biomarkers Among Integrin Subunits in the Skin Cutaneous Melanoma Microenvironment

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          Abstract

          The roles of different integrin alpha/beta (ITGA/ITGB) subunits in skin cutaneous melanoma (SKCM) and their underlying mechanisms of action remain unclear. Oncomine, UALCAN, GEPIA, STRING, GeneMANIA, cBioPortal, TIMER, TRRUST, and Webgestalt analysis tools were used. The expression levels of ITGA3, ITGA4, ITGA6, ITGA10, ITGB1, ITGB2, ITGB3, ITGB4, and ITGB7 were significantly increased in SKCM tissues. The expression levels of ITGA1, ITGA4, ITGA5, ITGA8, ITGA9, ITGA10, ITGB1, ITGB2, ITGB3, ITGB5, ITGB6 and ITGB7 were closely associated with SKCM metastasis. The expression levels of ITGA1, ITGA4, ITGB1, ITGB2, ITGB6, and ITGB7 were closely associated with the pathological stage of SKCM. The expression levels of ITGA6 and ITGB7 were closely associated with disease-free survival time in SKCM, and the expression levels of ITGA6, ITGA10, ITGB2, ITGB3, ITGB6, ITGB7, and ITGB8 were markedly associated with overall survival in SKCM. We also found significant correlations between the expression of integrin subunits and the infiltration of six types of immune cells (B cells, CD8+ T cells, CD4+T cells, macrophages, neutrophils, and dendritic cells). Finally, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed, and protein-protein interaction (PPI) networks were constructed. We have identified abnormally-expressed genes and gene regulatory networks associated with SKCM, improving understanding of the underlying pathogenesis of SKCM.

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          Most cited references63

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          The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data.

          The cBio Cancer Genomics Portal (http://cbioportal.org) is an open-access resource for interactive exploration of multidimensional cancer genomics data sets, currently providing access to data from more than 5,000 tumor samples from 20 cancer studies. The cBio Cancer Genomics Portal significantly lowers the barriers between complex genomic data and cancer researchers who want rapid, intuitive, and high-quality access to molecular profiles and clinical attributes from large-scale cancer genomics projects and empowers researchers to translate these rich data sets into biologic insights and clinical applications. © 2012 AACR.
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            TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells.

            Recent clinical successes of cancer immunotherapy necessitate the investigation of the interaction between malignant cells and the host immune system. However, elucidation of complex tumor-immune interactions presents major computational and experimental challenges. Here, we present Tumor Immune Estimation Resource (TIMER; cistrome.shinyapps.io/timer) to comprehensively investigate molecular characterization of tumor-immune interactions. Levels of six tumor-infiltrating immune subsets are precalculated for 10,897 tumors from 32 cancer types. TIMER provides 6 major analytic modules that allow users to interactively explore the associations between immune infiltrates and a wide spectrum of factors, including gene expression, clinical outcomes, somatic mutations, and somatic copy number alterations. TIMER provides a user-friendly web interface for dynamic analysis and visualization of these associations, which will be of broad utilities to cancer researchers. Cancer Res; 77(21); e108-10. ©2017 AACR.
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              UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses1

              Genomics data from The Cancer Genome Atlas (TCGA) project has led to the comprehensive molecular characterization of multiple cancer types. The large sample numbers in TCGA offer an excellent opportunity to address questions associated with tumo heterogeneity. Exploration of the data by cancer researchers and clinicians is imperative to unearth novel therapeutic/diagnostic biomarkers. Various computational tools have been developed to aid researchers in carrying out specific TCGA data analyses; however there is need for resources to facilitate the study of gene expression variations and survival associations across tumors. Here, we report UALCAN, an easy to use, interactive web-portal to perform to in-depth analyses of TCGA gene expression data. UALCAN uses TCGA level 3 RNA-seq and clinical data from 31 cancer types. The portal's user-friendly features allow to perform: 1) analyze relative expression of a query gene(s) across tumor and normal samples, as well as in various tumor sub-groups based on individual cancer stages, tumor grade, race, body weight or other clinicopathologic features, 2) estimate the effect of gene expression level and clinicopathologic features on patient survival; and 3) identify the top over- and under-expressed (up and down-regulated) genes in individual cancer types. This resource serves as a platform for in silico validation of target genes and for identifying tumor sub-group specific candidate biomarkers. Thus, UALCAN web-portal could be extremely helpful in accelerating cancer research. UALCAN is publicly available at http://ualcan.path.uab.edu.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                30 September 2021
                2021
                : 11
                : 751875
                Affiliations
                [1] Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine , Shanghai, China
                Author notes

                Edited by: Motoki Nakamura, Nagoya City University, Japan

                Reviewed by: Tetsuya Magara, Nagoya City University, Japan; Tadahiro Kobayashi, Kanazawa University, Japan

                *Correspondence: Heng Xu, xuh1990@ 123456gmail.com ; Yixin Zhang, zhangyixin6688@ 123456hotmail.com

                †These authors have contributed equally to this work and share first authorship

                This article was submitted to Skin Cancer, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2021.751875
                8514842
                34660316
                f4863d13-c7cd-4bb3-a052-94eb0765f2b4
                Copyright © 2021 Nurzat, Su, Min, Li, Xu and Zhang

                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
                : 02 August 2021
                : 09 September 2021
                Page count
                Figures: 9, Tables: 1, Equations: 0, References: 63, Pages: 16, Words: 4630
                Categories
                Oncology
                Original Research

                Oncology & Radiotherapy
                biomarkers,integrin subunit family,melanoma,skin cutaneous melanoma,cancer genome atlas

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