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CSMD1 Mutations Are Associated with Increased Mutational Burden, Favorable Prognosis, and Anti-Tumor Immunity in Gastric Cancer

Tumor mutational burden (TMB) is considered a potential biomarker for predicting the response and effect of immune checkpoint inhibitors (ICIs). To find specific gene mutations related to TMB and the prognosis of patients, the frequently mutated genes in gastric cancer patients from TCGA and ICGC we...

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Autores principales: Huang, Taobi, Liang, Yuan, Zhang, Huiyun, Chen, Xia, Wei, Hui, Sun, Weiming, Wang, Yuping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623648/
https://www.ncbi.nlm.nih.gov/pubmed/34828321
http://dx.doi.org/10.3390/genes12111715
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author Huang, Taobi
Liang, Yuan
Zhang, Huiyun
Chen, Xia
Wei, Hui
Sun, Weiming
Wang, Yuping
author_facet Huang, Taobi
Liang, Yuan
Zhang, Huiyun
Chen, Xia
Wei, Hui
Sun, Weiming
Wang, Yuping
author_sort Huang, Taobi
collection PubMed
description Tumor mutational burden (TMB) is considered a potential biomarker for predicting the response and effect of immune checkpoint inhibitors (ICIs). To find specific gene mutations related to TMB and the prognosis of patients, the frequently mutated genes in gastric cancer patients from TCGA and ICGC were obtained and the correlation between gene mutation, TMB, and prognosis was analyzed. Furthermore, to clarify whether specific gene mutations can be used as predictive biomarkers of ICIs, a gene set enrichment analysis (GSEA) for immune pathways and an immune infiltration analysis were conducted. The results showed that CUB and Sushi multiple domains 1 (CSMD1) mutation (CSMD1-mut) were associated with higher TMB and better prognosis in patients. The genetic map showed that, compared with wild-type samples, the loss of chromosomes 4q, 5q, 8p, and 9p decreased and the status of microsatellite instability increased in the CSMD1-mut samples. The GSEA analysis showed that immune-related pathways were enriched in the CSMD1-mut samples. The immune infiltration analysis showed that the anti-tumor immune cells were upregulated and that the tumor-promoting immune cells were downregulated in the CSMD1-mut samples. The gene co-expression analysis showed that PD-L1 expression was higher in the CSMD1-mut samples. In summary, CSMD1-mut in gastric cancer was associated with increased TMB and favorable survival and may have potential significance in predicting the efficacy of anti-PD-L1.
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spelling pubmed-86236482021-11-27 CSMD1 Mutations Are Associated with Increased Mutational Burden, Favorable Prognosis, and Anti-Tumor Immunity in Gastric Cancer Huang, Taobi Liang, Yuan Zhang, Huiyun Chen, Xia Wei, Hui Sun, Weiming Wang, Yuping Genes (Basel) Article Tumor mutational burden (TMB) is considered a potential biomarker for predicting the response and effect of immune checkpoint inhibitors (ICIs). To find specific gene mutations related to TMB and the prognosis of patients, the frequently mutated genes in gastric cancer patients from TCGA and ICGC were obtained and the correlation between gene mutation, TMB, and prognosis was analyzed. Furthermore, to clarify whether specific gene mutations can be used as predictive biomarkers of ICIs, a gene set enrichment analysis (GSEA) for immune pathways and an immune infiltration analysis were conducted. The results showed that CUB and Sushi multiple domains 1 (CSMD1) mutation (CSMD1-mut) were associated with higher TMB and better prognosis in patients. The genetic map showed that, compared with wild-type samples, the loss of chromosomes 4q, 5q, 8p, and 9p decreased and the status of microsatellite instability increased in the CSMD1-mut samples. The GSEA analysis showed that immune-related pathways were enriched in the CSMD1-mut samples. The immune infiltration analysis showed that the anti-tumor immune cells were upregulated and that the tumor-promoting immune cells were downregulated in the CSMD1-mut samples. The gene co-expression analysis showed that PD-L1 expression was higher in the CSMD1-mut samples. In summary, CSMD1-mut in gastric cancer was associated with increased TMB and favorable survival and may have potential significance in predicting the efficacy of anti-PD-L1. MDPI 2021-10-28 /pmc/articles/PMC8623648/ /pubmed/34828321 http://dx.doi.org/10.3390/genes12111715 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Huang, Taobi
Liang, Yuan
Zhang, Huiyun
Chen, Xia
Wei, Hui
Sun, Weiming
Wang, Yuping
CSMD1 Mutations Are Associated with Increased Mutational Burden, Favorable Prognosis, and Anti-Tumor Immunity in Gastric Cancer
title CSMD1 Mutations Are Associated with Increased Mutational Burden, Favorable Prognosis, and Anti-Tumor Immunity in Gastric Cancer
title_full CSMD1 Mutations Are Associated with Increased Mutational Burden, Favorable Prognosis, and Anti-Tumor Immunity in Gastric Cancer
title_fullStr CSMD1 Mutations Are Associated with Increased Mutational Burden, Favorable Prognosis, and Anti-Tumor Immunity in Gastric Cancer
title_full_unstemmed CSMD1 Mutations Are Associated with Increased Mutational Burden, Favorable Prognosis, and Anti-Tumor Immunity in Gastric Cancer
title_short CSMD1 Mutations Are Associated with Increased Mutational Burden, Favorable Prognosis, and Anti-Tumor Immunity in Gastric Cancer
title_sort csmd1 mutations are associated with increased mutational burden, favorable prognosis, and anti-tumor immunity in gastric cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623648/
https://www.ncbi.nlm.nih.gov/pubmed/34828321
http://dx.doi.org/10.3390/genes12111715
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