Construction of a prognostic model for gastric adenocarcinoma based on cellular senescence-related genes and analysis of immune microenvironment
10.3969/j.issn.1000-484X.2025.06.029
- VernacularTitle:基于细胞衰老相关基因构建胃腺癌预后模型及免疫微环境分析
- Author:
Yu LIU
1
;
Cheng ZENG
;
Min LIN
Author Information
1. 西安国际医学中心医院消化内科,西安 710001
- Publication Type:Journal Article
- Keywords:
Gastric adenocarcinoma;
Cellular senescence;
Prognostic model;
Immune microenvironment
- From:
Chinese Journal of Immunology
2025;41(6):1433-1439
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To construct a prognostic model related to cellular senescence in gastric adenocarcinoma by bioinforma-tics tools and analyze the immune microenvironment.Methods:Gene expression data and corresponding clinical information of gastric adenocarcinoma patients were downloaded from TCGA database.Cellular senescence-related genes(CSRGs)were downloaded from CellAge database.The limma package was used to screen for differentially expressed CSRGs in gastric adenocarcinoma tissues and the survival package was used to screen for CSRGs affecting the prognosis of gastric adenocarcinoma patients in R software.The LASSO regression analysis was used to construct a risk model for gastric adenocarcinoma and calculate the risk score for each patient.The Kaplan-Meier survival analysis was used to compare the overall survival(OS)of patients in high and low risk groups and the validity of prognostic models to predict 5-year survival of patients was analyzed by receiver operator characteristic curve(ROC).Univariate and multivariate Cox regression analyses were used to screen for independent prognostic factors in patients with gastric adenocarcinoma.Gene set enrichment analysis(GSEA)was used to predict potential signaling pathways in patients of high and low risk groups.Based on ESTIMATE and single sample gene set enrichment analysis(ssGSEA)algorithms to analyze the differences in tumor immune micro-environment between high and low risk groups of patients.Results:Sixteen prognostically relevant differentially expressed CSRGs were screened.The prognosis model of the genes containing AGT,EZH2,NOX4 and ZFP36 were constructed by LASSO regression analy-sis,and the patients were divided into two groups of high and low risk according to the median risk score.Survival analysis showed that patients in the high-risk group had significantly lower OS than those in the low-risk group.ROC curve analysis proved the accuracy of the prognostic model to predict the 5-year survival of patients(AUC=0.703).Then multifactorial Cox regression analysis suggested that age and risk score were independent prognostic factors for patients with gastric adenocarcinoma.GSEA enrichment analysis demonstrated that the high-risk group was associated with signaling pathways such as epithelial mesenchymal transition,hypoxia,and angiogenesis,while the low-risk group was associated with signaling pathways such as G2M checkpoint,DNA repair,and peroxisome.Further analy-sis showed that patients in the high-risk group had a higher abundance of immune cell infiltration and higher levels of immune check-point-related gene expression.Conclusion:In this study,a new prognostic model related to cellular senescence in gastric adenocarci-noma was constructed,in which patients in the high-risk group had higher immunoreactivity.
