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Significance of Tumor Mutation Burden Combined With Immune Infiltrates in the Progression and Prognosis of Advanced Gastric Cancer

Gastric cancer (GC) is a serious malignant tumor with high mortality and poor prognosis. The prognosis and survival are much worse for advanced gastric cancer (AGC). Recently, immunotherapy has been widely promoted for AGC patients, and studies have shown that tumor mutation burden (TMB) is closely...

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Autores principales: Guo, Xiong, Liang, Xiaolong, Wang, Yujun, Cheng, Anqi, Zhang, Han, Qin, Chuan, Wang, Ziwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299211/
https://www.ncbi.nlm.nih.gov/pubmed/34306002
http://dx.doi.org/10.3389/fgene.2021.642608
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author Guo, Xiong
Liang, Xiaolong
Wang, Yujun
Cheng, Anqi
Zhang, Han
Qin, Chuan
Wang, Ziwei
author_facet Guo, Xiong
Liang, Xiaolong
Wang, Yujun
Cheng, Anqi
Zhang, Han
Qin, Chuan
Wang, Ziwei
author_sort Guo, Xiong
collection PubMed
description Gastric cancer (GC) is a serious malignant tumor with high mortality and poor prognosis. The prognosis and survival are much worse for advanced gastric cancer (AGC). Recently, immunotherapy has been widely promoted for AGC patients, and studies have shown that tumor mutation burden (TMB) is closely related to immunotherapy response. Here, RNA-seq data, matched clinical information, and MAF files were downloaded from the cancer genome atlas (TCGA)-STAD project in the TCGA database. The collation and visual analysis of mutation data were implemented by the “maftools” package in R. We calculated the TMB values for AGC patients and divided the patients into high- and low-TMB groups according to the median value of TMB. Then, the correlation between high or low TMB and clinicopathological parameters was calculated. Next, we examined the differences in gene expression patterns between the two groups by using the “limma” R package and identified the immune-related genes among the DEGs. Through univariate Cox regression analysis, 15 genes related to prognosis were obtained. Furthermore, the two hub genes (APOD and SLC22A17) were used to construct a risk model to evaluate the prognosis of AGC patients. ROC and survival curves and GEO data were used as a validation set to verify the reliability of this risk model. In addition, the correlation between TMB and tumor-infiltrating immune cells was examined. In conclusion, our results suggest that AGC patients with high TMB have a better prognosis. By testing the patient’s TMB, we could better guide immunotherapy and understand patient response to immunotherapy.
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spelling pubmed-82992112021-07-24 Significance of Tumor Mutation Burden Combined With Immune Infiltrates in the Progression and Prognosis of Advanced Gastric Cancer Guo, Xiong Liang, Xiaolong Wang, Yujun Cheng, Anqi Zhang, Han Qin, Chuan Wang, Ziwei Front Genet Genetics Gastric cancer (GC) is a serious malignant tumor with high mortality and poor prognosis. The prognosis and survival are much worse for advanced gastric cancer (AGC). Recently, immunotherapy has been widely promoted for AGC patients, and studies have shown that tumor mutation burden (TMB) is closely related to immunotherapy response. Here, RNA-seq data, matched clinical information, and MAF files were downloaded from the cancer genome atlas (TCGA)-STAD project in the TCGA database. The collation and visual analysis of mutation data were implemented by the “maftools” package in R. We calculated the TMB values for AGC patients and divided the patients into high- and low-TMB groups according to the median value of TMB. Then, the correlation between high or low TMB and clinicopathological parameters was calculated. Next, we examined the differences in gene expression patterns between the two groups by using the “limma” R package and identified the immune-related genes among the DEGs. Through univariate Cox regression analysis, 15 genes related to prognosis were obtained. Furthermore, the two hub genes (APOD and SLC22A17) were used to construct a risk model to evaluate the prognosis of AGC patients. ROC and survival curves and GEO data were used as a validation set to verify the reliability of this risk model. In addition, the correlation between TMB and tumor-infiltrating immune cells was examined. In conclusion, our results suggest that AGC patients with high TMB have a better prognosis. By testing the patient’s TMB, we could better guide immunotherapy and understand patient response to immunotherapy. Frontiers Media S.A. 2021-07-09 /pmc/articles/PMC8299211/ /pubmed/34306002 http://dx.doi.org/10.3389/fgene.2021.642608 Text en Copyright © 2021 Guo, Liang, Wang, Cheng, Zhang, Qin and Wang. 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
Guo, Xiong
Liang, Xiaolong
Wang, Yujun
Cheng, Anqi
Zhang, Han
Qin, Chuan
Wang, Ziwei
Significance of Tumor Mutation Burden Combined With Immune Infiltrates in the Progression and Prognosis of Advanced Gastric Cancer
title Significance of Tumor Mutation Burden Combined With Immune Infiltrates in the Progression and Prognosis of Advanced Gastric Cancer
title_full Significance of Tumor Mutation Burden Combined With Immune Infiltrates in the Progression and Prognosis of Advanced Gastric Cancer
title_fullStr Significance of Tumor Mutation Burden Combined With Immune Infiltrates in the Progression and Prognosis of Advanced Gastric Cancer
title_full_unstemmed Significance of Tumor Mutation Burden Combined With Immune Infiltrates in the Progression and Prognosis of Advanced Gastric Cancer
title_short Significance of Tumor Mutation Burden Combined With Immune Infiltrates in the Progression and Prognosis of Advanced Gastric Cancer
title_sort significance of tumor mutation burden combined with immune infiltrates in the progression and prognosis of advanced gastric cancer
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299211/
https://www.ncbi.nlm.nih.gov/pubmed/34306002
http://dx.doi.org/10.3389/fgene.2021.642608
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