胃癌预后生物标志物TSC2及其与免疫浸润的相关性分析  

Prognostic biomarker TSC2 in gastric cancer and its correlation with immune infiltration

作　　者：陈亚文 高云鹤 乔治 Chen Yawen;Gao Yunhe;Qiao Zhi(Department of General Surgery,the First Medical Center,Chinese PLA General Hospital,Beijing 100853,China)

机构地区：[1]中国人民解放军总医院第一医学中心普通外科医学部,北京100853

出　　处：《国际外科学杂志》2025年第1期51-57,I0008-I0013,共13页International Journal of Surgery

基　　金：军队保障课题(24BJZ15)。

摘　　要：目的:探讨TSC2在胃癌中的表达及其与预后价值及免疫浸润的相关性。方法:通过生物信息学和实验验证,分析来自癌症基因组图谱(TCGA)数据库的TCGA-STAD数据集和TCGA_GTEx-STAD数据集(包含624例胃癌患者的RNA测序数据),并从人类蛋白质图谱数据库(HPA)下载了在正常组织和胃癌组织中表达的免疫组化(IHC)图像,评估胃癌中TSC2的表达与临床病理特征、预后、免疫浸润和免疫亚型之间的相关性。通过定量实时PCR(qRT-PCR)检测胃细胞系中TSC2的表达。采用SPSS26.0和R4.2.1软件进行统计分析。结果:与正常组织相比,胃癌组织和细胞系中TSC2的表达显著下调。TSC2表达水平低与胃癌患者的总生存期、首次进展和进展无病生存期较差相关。TSC2表达与B细胞、CD8^(+)T细胞、CD4^(+)T细胞和巨噬细胞的浸润水平呈正相关,但与NK细胞和嗜酸性粒细胞呈负相关。功能富集分析表明,TSC2与细胞周期调节、蛋白质转运和免疫反应相关的通路相关。TSC2表达还与胃癌中的不同免疫亚型相关。结论:TSC2表达在胃癌中下调,并与预后不良和免疫浸润相关。TSC2可能作为胃癌的潜在预后生物标志物和治疗靶点。Objective:To investigate the expression of TSC2 in gastric cancer and its correlation with prognostic value and immune infiltration.Methods:Through Utilizing bioinformatics and experimental validation,analyzed RNA sequencing data from 624 gastric cancer patients in the TCGA-STAD dataset and the TCGA-GTEx-STAD dataset from the Cancer Genome Atlas(TCGA)database.Immunohistochemical(IHC)images of TSC2 expression in normal and gastric cancer tissues were obtained from the Human Protein Atlas(HPA).Evaluated the relationship between TSC2 expression and clinicopathological features,prognosis,immune infiltration,and immune subtypes in gastric cancer.Additionally,the expression of TSC2 in gastric cell lines was assessed by quantitative real-time PCR(qRT-PCR).Statistical analysis was conducted using SPSS 26.0 and R4.2.1 software.Results:TSC2 expression was significantly downregulated in gastric cancer tissues and cell lines compared to normal tissues.Lower expression of TSC2 correlated with worse overall survival,first progression,and progression-free survival in gastric cancer patients.TSC2 expression positively correlated with the infiltration levels of B cells,CD8^(+)T cells,CD4^(+)T cells,and macrophages,while it negatively correlated with the levels of NK cells and eosinophils.Functional enrichment analysis indicated that TSC2 was involved in pathways related to cell cycle regulation,protein transport,and immune response.TSC2 expression also associated with different immune subtypes within gastric cancer.Conclusions:TSC2 expression is downregulated in gastric cancer and is associated with poor prognosis and immune infiltration.TSC2 may act as a potential prognostic biomarker and a therapeutic target for gastric cancer.

关 键 词：胃肿瘤 基因表达 生物学标记 预后 免疫 

分 类 号：R73[医药卫生—肿瘤]