Author:
Yue Taohua,Zuo Shuai,Zhu Jing,Guo Shihao,Huang Zhihao,Li Jichang,Wang Xin,Liu Yucun,Chen Shanwen,Wang Pengyuan
Abstract
BackgroundGlobally, stomach adenocarcinoma (STAD)’s high morbidity and mortality should arouse our urgent attention. How long can STAD patients survive after surgery and whether novel immunotherapy is effective are questions that our clinicians cannot escape.MethodsVarious R packages, GSEA software, Metascape, STRING, Cytoscape, Venn diagram, TIMER2.0 website, TCGA, and GEO databases were used in our study.ResultsIn the TCGA and GEO, macrophage abundance of STAD tissues was significantly higher than that of adjacent tissues and was an independent prognostic factor, significantly related to the overall survival (OS) of STAD patients. Between the high- and low- macrophage abundance, we conducted differential expression, univariate and multivariate Cox analysis, and obtained 12 candidate genes, and finally constructed a 3-gene signature. Both low macrophage abundance group and group D had higher TMB and PD-L1 expression. Furthermore, top 5 common gene-mutated STAD tissues had lower macrophage abundance. Macrophage abundance and 3 key genes expression were also lower in the Epstein-Barr Virus (EBV) and HM-indel STAD subtypes and significantly correlated with the tumor microenvironment score. The functional enrichment and ssGSEA revealed 2 signatures were similar and closely related to BOQUEST_STEM_CELL_UP, including genes up-regulated in proliferative stromal stem cells. Hsa-miR-335-5p simultaneously regulated 3 key genes and significantly related to the expression of PD-L1, CD8A and PDCD1.Conclusionmacrophage abundance and 3-gene signature could simultaneously predict the OS and immunotherapy efficacy, and both 2 signatures had remarkable similarities. Hsa-miR-335-5p and BOQUEST_STEM_CELL_UP might be novel immunotherapy targets.
Funder
Foundation for Innovative Research Groups of the National Natural Science Foundation of China
National Major Science and Technology Projects of China
Subject
Cell Biology,Developmental Biology
Cited by
5 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献