基于生物信息学分析泛凋亡基因对胃癌预后及肿瘤免疫微环境的影响  

Identification of gastric cancer subtypes and immune characteristics based on PANoptosis-related genes

作　　者：魏相相 魏秋亚 张栋岩 雍桃 邓成伍 王琛[1,2] Wei Xiangxiang;Wei Qiuya;Zhang Dongyan;Yong Tao;Deng Chengwu;Wang Chen(The Second Clinical Medical School,Lanzhou University,Lanzhou 730030,China;Department of General Surgery,The Second Hospital of Lanzhou University,Lanzhou 730030,China)

机构地区：[1]兰州大学第二临床医学院,甘肃兰州730030 [2]兰州大学第二医院普外科,甘肃兰州730030

出　　处：《兰州大学学报（医学版）》2024年第2期39-47,54,共10页Journal of Lanzhou University（Medical Sciences）

基　　金：兰州大学第二医院“萃英科技创新”计划资助项目(CY-2022-BJ-06);甘肃省科技计划资助项目(21JR7RA433);兰州大学第二医院“萃英科技创新”计划资助项目(CY2020-MS22)。

摘　　要：目的探讨泛凋亡相关基因对胃癌患者预后及免疫微环境的预测价值。方法基于TCGA、GEO数据库中胃癌患者PANoptosis差异基因表达谱,对胃癌患者进行聚类分析并构建预测模型,分析不同胃癌患者PANoptosis亚型及高、低风险组间肿瘤免疫微环境差异。结果胃癌患者可分为两个PANoptosis分子亚型,亚型间患者的临床特征、预后、信号通路和肿瘤微环境有显著差异。根据PANoptosis相关基因在胃癌组织中的表达水平,经Lasso回归分析、多因素Cox回归分析,鉴定出6个关键基因(IRF2、AKT3、UNC5B、CYCS、CASP5、TICAM1)用于构建风险评分体系。多组学分析发现,风险评分与微卫星不稳定性、肿瘤突变负荷和肿瘤干细胞指数呈负相关关系。基于PANoptosis风险评分和临床病理因素构建诺莫图,预测胃癌患者1、3、5年生存率的受试者操作特征曲线下面积值分别为0.702、0.736、0.744。实时定量聚合酶链式反应实验证实风险基因CYCS、CASP5、TICAM1在胃癌细胞系中高表达(P<0.01)。结论基于胃癌PANoptosis相关基因构建的预后模型有望成为独立预测胃癌患者预后的指标。Objective To investigate the predictive value of PANoptosis related genes on prognosis and immune microenvironment in patients with gastric cancer.Methods Based on the differential gene expression profile of PANoptosis in TCGA and GEO databases,a cluster analysis was performed in gastric cancer patients and prediction models constructed to analyze the differences in tumor immune microenvironment between different subtypes of PANoptosis and high and low risk groups in gastric cancer patients.Results Gastric cancer patients could be divided into two PANoptosis subtypes,and there were significant differences in clinical features,prognosis,pathways and tumor microenvironment between them.Acorrding to the expression levels of PANoptosis related-genes in gastric cancer tissues,and six key genes(IRF2,AKT3,UNC5B,CYCS,CASP5,TICAM1)were identified by multivariate Cox analysis and Lasso analysis to build a risk scoring system.Multi-omics analysis found that risk scores were negatively correlated with microsatellite instability,tumor mutation load,and cancer stem cell index.Based on the PANoptosis risk scores and clinicopathological factors,the 1-year,3-year and 5-year survival rates of gastric cancer patients were predicted to be 0.702,0.736 and 0.744.qRT-PCR confirmed that risk genes CYCS,CASP5 and TICAM1 were highly expressed in gastric cancer cell lines(P<0.01).Conclusions The prognostic model based on PANoptosis related genes of gastric cancer is expected to be an independent prognostic indicator for patients with gastric cancer.

关 键 词：胃癌 泛凋亡 分子亚型 预测模型 免疫微环境 生物信息学 

分 类 号：R735.2[医药卫生—肿瘤]