ARHGAP10基因在透明细胞肾癌中的表达水平、预后影响以及免疫作用  

Expression,prognosis,and immune function of ARHGAP10 gene in clear cell renal cell carcinoma

作　　者：何虎 陈强 潘进洪 朱建国[2] He Hu;Chen Qiang;Pan Jinhong;Zhu Jianguo(Department of Urology,Guizhou International General Hospital,Guiyang 550018,China;Department of Urology,Guizhou Provincial People′s Hospital,Guiyang 550000,China)

机构地区：[1]贵黔国际总医院泌尿外科,贵阳550018 [2]贵州省人民医院泌尿外科,贵阳550000

出　　处：《国际泌尿系统杂志》2024年第5期863-869,共7页International Journal of Urology and Nephrology

基　　金：2018年贵州省高层次创新人才项目([2018]5639);2019年贵阳市科技计划项目([2019]2-15);2019年贵州省科技计划项目([2019]1203)。

摘　　要：目的探讨ARHGAP10基因在透明细胞肾癌(ccRCC)中的表达水平、预后影响以及免疫作用。方法通过检测癌症基因组图谱(TCGA)数据中ccRCC组织和正常邻近组织中的ARHGAP10表达水平,将所有患者随机分为低表达组(269例)和高表达组(270例)。同时通过TIMER数据库验证ARHGAP10的差异表达。采用多变量方法和Kaplan-Meier生存曲线评估ARHGAP表达与临床病理参数和总生存期(OS)的关系。ARHGAP10与相互作用的蛋白质网络使用在线STRING网站构建。使用TIMER和GEPIA数据库研究ARHGAP10表达与浸润免疫细胞及其相应基因标记组之间的关系。结果低表达组和高表达组的年龄、组织学分级、病理分期、OS等资料比较,差异均有统计学意义(均P<0.05)。在TCGA数据库中,与正常组织相比,肿瘤组织中的ARHGAP10基因表达水平显著升高。ARHGAP10基因表达水平与性别、病理分期无相关性(均P>0.05),而与肿瘤浸润深度和是否远处转移具有显著相关性(均P<0.05)。ARHGAP10基因低表达的ccRCC患者在测试队列中表示出较短的OS(P<0.001)。单因素Cox分析结果显示,ARHGAP10表达与病理学阶段、组织学分级、年龄等都具有显著相关性(均P<0.001)。多变量Cox分析结果显示,ARHGAP10表达与年龄、肿瘤浸润深度、远处转移也显著相关(均P<0.05)。ARHGAP10的表达水平与ccRCC中CD4^(+)T细胞(r=0.32)、CD8^(+)T细胞(r=0.224)、巨噬细胞(r=0.218)、嗜中性粒细胞(r=0.155)和树突状细胞(r=0.133)的浸润水平呈明显正相关(均P<0.05),但与肿瘤纯度和B细胞无关(均P>0.05)。结论ARHGAP10表达不足与ccRCC的进展、预后不良和免疫细胞浸润受损有关。ObjectiveTo investigate the expression,prognosis,and immune function of ARHGAP10 gene in clear cell renal cell carcinoma(ccRCC).MethodsBy measuring ARHGAP10 expression in ccRCC tissue and normal adjacent tissue in Cancer Genome Atlas(TCGA)data,all patients were randomly divided into a low expression group(269 cases)and a high expression group(270 cases).Meanwhile,the differential expression of ARHGAP10 was verified by the TIMER database.The relationship between ARHGAP expression and clinicopathological parameters and overall survival(OS)was evaluated using multivariate methods and Kaplan-Meier survival curve.ARHGAP10 was constructed with a network of interacting proteins using an online STRING website.TIMER and GEPIA databases were used to study the relationship between ARHGAP10 expression and infiltrating immune cells and their corresponding gene markers.ResultsThere were significant differences in age,histological grade,pathological stage and OS between low expression group and high expression group(all P<0.05).In the TCGA database,the expression level of ARHGAP10 gene in tumor tissues was significantly higher than that in normal tissues.The expression level of ARHGAP10 gene was not correlated with gender and pathological stage(all P>0.05),but was significantly correlated with tumor invasion depth and distant metastasis(all P<0.05).ccRCC patients with lower ARHGAP10 mRNA expression showed shorter OS in the test cohort(P<0.001).Univariate Cox analysis showed that ARHGAP10 expression was significantly correlated with pathological stage,histological grade and age(all P<0.001).The results of multivariate Cox analysis showed that ARHGAP10 expression was also significantly correlated with age and degree of tumor invasion and distant metastasis(all P<0.05).The expression level of ARHGAP10 was significantly positively correlated that of CD4^(+)T cells(r=0.32),CD8^(+)T cells(r=0.224),macrophages(r=0.218),neutrophils(r=0.155)and dendritic cells(r=0.133)in ccRCC(all P<0.05),but not with tumor purity and B cells(all P>0.05

关 键 词：癌 肾细胞 ARHGAP10 基因 生物标志物 

分 类 号：R737.11[医药卫生—肿瘤]