胃癌炎症基因THY1表达及其与肿瘤免疫和上皮-间充质转化的关系  

Expression of inflammatory related gene THY1 in gastric cancer and its relationship with tumor immunity and epithelial-mesenchymal transition

作　　者：李兆星[1] 檀碧波[1] 张志栋[1] 刘庆伟[1] 谭明[1] 郭洪海[1] 苑新宇 王骁[2] 李勇[1] Li Zhaoxing;Tan Bibo;Zhang Zhidong;Liu Qingwei;Tan Ming;Guo Honghai;Yuan Xinyu;Wang Xiao;Li Yong(Third Department of Surgery,the Fourth Hospital of Hebei Medical University,Shijiazhuang 050011,China;Second Department of Oncology,Hebei Provincial Hospital of Traditional Chinese Medicine,Shijiazhuang 050000,China)

机构地区：[1]河北医科大学第四医院外三科,石家庄050011 [2]河北省中医院肿瘤二科,石家庄050000

出　　处：《中华实验外科杂志》2024年第4期720-723,共4页Chinese Journal of Experimental Surgery

基　　金：河北省重点研发计划项目(22377701D);政府资助临床优秀人才培养项目(ZF2024166)。

摘　　要：目的基于生物信息学分析方法探讨炎症基因THY1在胃癌中表达、预后价值及其与肿瘤免疫、上皮-间充质转化(EMT)的关系。方法在癌症基因组图谱数据库(TCGA)中生成胃癌和正常组织数据集,筛选在胃癌中存在差异表达炎症相关基因,采用wilcoxon.test方法识别差异表达基因(DEGs),校正后P<0.05且表达变化超过1.5倍的基因被鉴定为DEGs,确定THY1进行研究。使用R软件的生存分析功能(survival)确定THY1表达的预后评估价值;应用Metascape数据库对THY1功能进行富集分析;在TIMER 2.0数据库研究THY1基因表达与免疫细胞丰度相关性;使用STRING数据库分析与THY1存在互相作用的蛋白质,分析蛋白互作(PPI)结果。取20例新鲜胃癌组织及癌旁组织,使用荧光实时定量反转录聚合酶链反应(RT-qPCR)检测各基因的mRNA水平。网络数据使用R软件进行生物信息学分析;组织的RT-qPCR检测结果采用配对样本的t检验。结果162个炎症相关基因中,30个在胃癌组织中表达高于癌旁组织,32个低于癌旁组织(P<0.05),选择THY1为研究基因。THY1在胃癌中表达水平(18.60±1.16)与正常组织(16.98±1.31)比较,差异有统计学意义(W=10017,P<0.01);根据THY1中位数将患者分为高表达组与低表达组,Kaplan-Meier生存结果显示高表达组中位生存期明显短于低表达组(χ^(2)=5.62,P<0.05)。对THY1基因功能富集分析结果显示其功能与Ephrin受体信号通路、细胞黏附调节、白细胞介导的细胞毒反应等有关。THY1表达与T细胞CD4+CD8+丰度正相关。应用THY1表达的中位数将样本分组,应用wilcoxon.test识别DEGs并进行GSEA富集分析,结果显示DEGs富集到EMT和炎性反应过程。PPI结果显示,THY1蛋白与纤维连接蛋白1(FN1)、促红细胞生成素产生肝细胞受体A4(EPHA4)等蛋白质存在互作。对临床组织检测结果显示,THY1、FN1、EPHA4的mRNA表达在胃癌组织(4.668±3.449、8.382±2.093、1.647±0.294)均高于癌旁组�Objective To investigate the expression and prognostic value of inflammatory gene THY1 in gastric cancer,and the relationship between THY1 and tumor immunity,epithelial-mesenchymal transition(EMT)based on bioinformatics analysis.Methods Data sets of gastric cancer and normal tissues were generated from the cancer genome atlas(TCGA)database,and inflammation-related genes that were differentially expressed in gastric cancer were screened.The differentially expressed genes(DEGs)were identified by wilcoxon.test method,and after correction,genes with P<0.05 and expression change over 1.5 times were identified as DEGs,then THY1 was identified for subsequent study.Survival analysis function of R software package was used to determine the prognostic value of THY1 expression.Function of THY1 was enriched by Metascape database.The correlation between the expression of THY1 gene and the abundance of immune cells was investigated in TIMER 2.0 database.Proteins interacting with THY1 were analyzed using STRING database,and the protein-protein interaction(PPI)results were analyzed.The mRNA levels of each gene were detected by fluorescence real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR)in 20 cases of fresh gastric cancer tissues and adjacent tissues.The network data were analyzed using R software for bioinformatics.The RT-qPCR detection results of tissues were processed by SPSS 25.0 software,t-test of paired samples was used,and P<0.05 was considered statistically significant.Results Among the 162 inflammation-related genes,30 were up-regulated in gastric cancer tissues compared to adjacent tissues,and 32 were down-regulated(P<0.05),and THY1 was determined as the research object.The expression of THY1 in gastric cancer tissues(18.60±1.16)was significantly higher than that in normal tissues(16.98±1.31,W=10017,P<0.01).According to the median of THY1,patients were divided into high expression group and low expression group.Kaplan-Meier survival results showed that the median survival time in the hi

关 键 词：胃癌 THY1基因 炎性反应 肿瘤免疫 上皮-间充质转化 

分 类 号：R735.2[医药卫生—肿瘤]