文献类型：期刊文献

英文题名：Identification of a Gene Prognostic Model of Gastric Cancer Based on Analysis of Tumor Mutation Burden

作者：Ma, Weijun[1,2];Li, Weidong[1,2];Xu, Lei[2,3];Liu, Lu[2,3];Xia, Yu[2,4];Yang, Liping[2];Da, Mingxu[1,2]

第一作者：Ma, Weijun

通信作者：Da, MX[1];Yang, LP[2];Da, MX[2]

机构：[1]Ningxia Med Univ, Sch Clin Med, Yinchuan, Ningxia, Peoples R China;[2]Gansu Prov Hosp, Dept Surg Oncol, Lanzhou, Peoples R China;[3]Gansu Univ Chinese Med, Gansu Prov Hosp, Clin Med Coll 1, Lanzhou, Gansu, Peoples R China;[4]Lanzhou Univ, Clin Med Sch 1, Lanzhou, Peoples R China

第一机构：Ningxia Med Univ, Sch Clin Med, Yinchuan, Ningxia, Peoples R China

通信机构：[1]corresponding author), Ningxia Med Univ, Sch Clin Med, Yinchuan, Ningxia, Peoples R China;[2]corresponding author), Gansu Prov Hosp, Dept Surg Oncol, Lanzhou, Peoples R China.

年份：2021

卷号：27

外文期刊名：PATHOLOGY & ONCOLOGY RESEARCH

收录：;Scopus(收录号：2-s2.0-85115714096);WOS:【SCI-EXPANDED(收录号:WOS:000698547900001)】；

基金：This work is supported by Grants from the Natural Science Foundation Project of Gansu Provincial Science and Technology Department (No.18JR3RA334).

语种：英文

外文关键词：prognosis; gastric cancer; TCGA; immune infiltration; tumor mutation burden

摘要：Introduction: Gastric cancer is one of the most common cancers. Although some progress has been made in the treatment of gastric cancer with the improvement of surgical methods and the application of immunotherapy, the prognosis of gastric cancer patients is still unsatisfactory. In recent years, there has been increasing evidence that tumor mutational load (TMB) is strongly associated with survival outcomes and response to immunotherapy. Given the variable response of patients to immunotherapy, it is important to investigate clinical significance of TMB and explore appropriate biomarkers of prognosis in patients with gastric cancer (GC).

Material and Methods: All data of patients with gastric cancer were obtained from the database of The Cancer Genome Atlas (TCGA). Samples were divided into two groups based on median TMB. Differently expressed genes (DEGs) between the high- and low-TMB groups were identified and further analyzed. We identified TMB-related genes using Lasso, univariate and multivariate Cox regression analysis and validated the survival result of 11 hub genes using Kaplan-Meier Plotter. In addition, "CIBERSORT" package was utilized to estimate the immune infiltration.

Results: Single nucleotide polymorphism (SNP), C > T transition were the most common variant type and single nucleotide variant (SNV), respectively. Patients in the high-TMB group had better survival outcomes than those in the low-TMB group. Besides, eleven TMB-related DEGs were utilized to construct a prognostic model that could be an independent risk factor to predict the prognosis of patients with GC. What's more, the infiltration levels of CD4(+) memory-activated T cells, M0 and M1 macrophages were significantly increased in the high-TMB group compared with the low-TMB group.

Conclusions: Herein, we found that patients with high TMB had better survival outcomes in GC. In addition, higher TMB might promote immune infiltration, which could provide new ideas for immunotherapy.