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USH2A Mutation is Associated With Tumor Mutation Burden and Antitumor Immunity in Patients With Colon Adenocarcinoma

Colon adenocarcinoma (COAD) is one of the diseases with the highest morbidity and mortality in the world. At present, immunotherapy has become a valuable method for the treatment of COAD. Tumor mutational burden (TMB) is considered to be the most common biomarker for predicting immunotherapy. Accord...

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Autores principales: Sun, Yuanyuan, Li, Long, Yao, Wenchao, Liu, Xuxu, Yang, Yang, Ma, Biao, Xue, Dongbo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8593250/
https://www.ncbi.nlm.nih.gov/pubmed/34795697
http://dx.doi.org/10.3389/fgene.2021.762160
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author Sun, Yuanyuan
Li, Long
Yao, Wenchao
Liu, Xuxu
Yang, Yang
Ma, Biao
Xue, Dongbo
author_facet Sun, Yuanyuan
Li, Long
Yao, Wenchao
Liu, Xuxu
Yang, Yang
Ma, Biao
Xue, Dongbo
author_sort Sun, Yuanyuan
collection PubMed
description Colon adenocarcinoma (COAD) is one of the diseases with the highest morbidity and mortality in the world. At present, immunotherapy has become a valuable method for the treatment of COAD. Tumor mutational burden (TMB) is considered to be the most common biomarker for predicting immunotherapy. According to reports, the mutation rate of COAD ranks third. However, whether these gene mutations are related to TMB and immune response is still unknown. Here, COAD somatic mutation data were downloaded from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Bioinformatics methods were used to study the relationships among gene mutations, COAD survival prognosis, and tumor immune response. A total of 22 of the top 40 mutations in TCGA and ICGC databases were the same. Among them, the USH2A mutation was associated with high TMB and poor clinical prognosis. According to Gene Set Enrichment Analysis (GSEA) and the CIBERSORT algorithm, we determined that the USH2A mutation upregulates signaling pathways involved in the immune system and the antitumor immune response. In cases with a USH2A mutation, the immune score and MSI score of TCGA samples increased, the expression of immune checkpoint genes decreased significantly, and the TIDE score decreased significantly. Dependent on the presence or absence of a USH2A mutation, TCGA COAD samples were analyzed for differentially expressed genes, 522 of which were identified. Using a univariate Cox analysis and LASSO COX analysis of these differential genes, a prediction model was established, which established significant differences in the infiltration of immune cells, immune checkpoint gene expression, immune score, MSI score, TMB, and TIDE in patients in high- and low-risk groups. In conclusion, mutation of USH2A is frequent in COAD and is related to an increase in TMB and the antitumor immunity. The differential genes screened by USH2A mutation allowed the construction of a risk model for predicting the survival and prognosis of cancer patients, in addition to providing new ideas for COAD immunotherapy.
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spelling pubmed-85932502021-11-17 USH2A Mutation is Associated With Tumor Mutation Burden and Antitumor Immunity in Patients With Colon Adenocarcinoma Sun, Yuanyuan Li, Long Yao, Wenchao Liu, Xuxu Yang, Yang Ma, Biao Xue, Dongbo Front Genet Genetics Colon adenocarcinoma (COAD) is one of the diseases with the highest morbidity and mortality in the world. At present, immunotherapy has become a valuable method for the treatment of COAD. Tumor mutational burden (TMB) is considered to be the most common biomarker for predicting immunotherapy. According to reports, the mutation rate of COAD ranks third. However, whether these gene mutations are related to TMB and immune response is still unknown. Here, COAD somatic mutation data were downloaded from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Bioinformatics methods were used to study the relationships among gene mutations, COAD survival prognosis, and tumor immune response. A total of 22 of the top 40 mutations in TCGA and ICGC databases were the same. Among them, the USH2A mutation was associated with high TMB and poor clinical prognosis. According to Gene Set Enrichment Analysis (GSEA) and the CIBERSORT algorithm, we determined that the USH2A mutation upregulates signaling pathways involved in the immune system and the antitumor immune response. In cases with a USH2A mutation, the immune score and MSI score of TCGA samples increased, the expression of immune checkpoint genes decreased significantly, and the TIDE score decreased significantly. Dependent on the presence or absence of a USH2A mutation, TCGA COAD samples were analyzed for differentially expressed genes, 522 of which were identified. Using a univariate Cox analysis and LASSO COX analysis of these differential genes, a prediction model was established, which established significant differences in the infiltration of immune cells, immune checkpoint gene expression, immune score, MSI score, TMB, and TIDE in patients in high- and low-risk groups. In conclusion, mutation of USH2A is frequent in COAD and is related to an increase in TMB and the antitumor immunity. The differential genes screened by USH2A mutation allowed the construction of a risk model for predicting the survival and prognosis of cancer patients, in addition to providing new ideas for COAD immunotherapy. Frontiers Media S.A. 2021-11-02 /pmc/articles/PMC8593250/ /pubmed/34795697 http://dx.doi.org/10.3389/fgene.2021.762160 Text en Copyright © 2021 Sun, Li, Yao, Liu, Yang, Ma and Xue. https://creativecommons.org/licenses/by/4.0/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.
spellingShingle Genetics
Sun, Yuanyuan
Li, Long
Yao, Wenchao
Liu, Xuxu
Yang, Yang
Ma, Biao
Xue, Dongbo
USH2A Mutation is Associated With Tumor Mutation Burden and Antitumor Immunity in Patients With Colon Adenocarcinoma
title USH2A Mutation is Associated With Tumor Mutation Burden and Antitumor Immunity in Patients With Colon Adenocarcinoma
title_full USH2A Mutation is Associated With Tumor Mutation Burden and Antitumor Immunity in Patients With Colon Adenocarcinoma
title_fullStr USH2A Mutation is Associated With Tumor Mutation Burden and Antitumor Immunity in Patients With Colon Adenocarcinoma
title_full_unstemmed USH2A Mutation is Associated With Tumor Mutation Burden and Antitumor Immunity in Patients With Colon Adenocarcinoma
title_short USH2A Mutation is Associated With Tumor Mutation Burden and Antitumor Immunity in Patients With Colon Adenocarcinoma
title_sort ush2a mutation is associated with tumor mutation burden and antitumor immunity in patients with colon adenocarcinoma
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8593250/
https://www.ncbi.nlm.nih.gov/pubmed/34795697
http://dx.doi.org/10.3389/fgene.2021.762160
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