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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8623648 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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