ARL4C在脑胶质瘤中的表达及其临床意义

Expression and clinical significance of ARL4C in gliomas

目的探讨ADP-核糖基化样因子4C(ARL4C)在脑胶质瘤中的表达水平及其临床意义。方法回顾性分析来自中国脑胶质瘤基因组图谱(CGGA)数据库(325例)和癌症基因组图谱(TCGA)数据库(609例)的胶质瘤患者的临床资料。选取45例来源于2013年7月至2016年12月首都医科大学附属北京天坛医院神经外科的胶质瘤手术标本,分别采用反转录聚合酶链反应(RT-PCR)和免疫组织化学染色方法检测肿瘤组织中ARL4C的表达水平。基于数据库资料和45例胶质瘤手术患者的数据,应用单因素分析和多因素Cox回归分析探讨肿瘤组织中ARL4C的表达水平与其病理学分级以及患者总体生存期的关系。结果CGGA数据库和TCGA数据库分析结果显示:(1)ARL4C的表达水平随胶质瘤世界卫生组织(WHO)分级的升高而增加(均P<0.001);(2)与低表达ARL4C的患者相比,高表达ARL4C的患者异柠檬酸脱氢酶突变率更低,而年龄偏高(均P<0.001);(3)多因素Cox回归分析结果显示,ARL4C的表达与胶质瘤患者的不良预后有关,ARL4C高表达组的总生存期较ARL4C低表达组短(均P<0.001)。45例脑胶质瘤患者数据的分析结果显示:(1)ARL4C的基因表达水平随WHO分级的升高而增加(P=0.013);免疫组织化学染色结果证实,ARL4C蛋白的表达具有同一趋势(P=0.001);(2)高表达ARL4C患者的生存期短于低表达ARL4C患者(HR=2.590,95%CI:1.193~5.621,P=0.016)。结论脑胶质瘤中的ARL4C表达水平与肿瘤病理学级别有关,高表达ARL4C的患者预后不良。ARL4C可能成为脑胶质瘤治疗和预后评估的新靶点。

Objective To investigate the expression level of ADP-ribosylation-like factor 4C(ARL4C)in gliomas and its clinical significance.Methods Clinical data of 325 patients with gliomas from Chinese Glioma Genome Atlas(CGGA)and 609 patients with gliomas from The Cancer Genome Atlas(TCGA)databases were retrospectively analyzed.Specimens from additional independent 45 cases of gliomas admitted to Department of Neurosurgery,Beijing Tiantan Hospital,Capital Medical University were used in this study,and the expression level of ARL4C from the tumor specimen was determined both by RT-PCR and immunohistochemistry.Based on the database and 45 glioma patients’data,univariate analysis and multivariate Cox analysis were used to explore the relationship between the expression level of ARL4C and pathological grade and overall survival(OS)of patients.Results The analysis results of CGGA and TCGA database were as follows:(1)The expression level of ARL4C was elevated with the increase of pathological grade(all P<0.001);(2)Compared with ARL4C low-expression patients,ARL4C high-expression patients had lower IDH mutation ratio and older ages(all P<0.001)in both CGGA and TCGA database;(3)Multivariate Cox analysis showed that the expression level of ARL4C was related to the poor outcomes,and OS in patients with high expression levels of ARL4C was shorter than that in those with low ARL4C levels(both P<0.001).The analysis results from the tumor specimens from 45 patients were as follows:(1)RT-PCR experiment showed that the mRNA expression level of ARL4C in gliomas was elevated with the increase of pathological grades(P=0.013),and immunohistochemistry experiment validated the same trend(P=0.001);(2)The OS of high-ARL4C patients was shorter than that of ARL4C low-expression patients(HR=2.590,95%CI:1.193-5.621,P=0.016).Conclusions The expression level of ARL4C in glioma seems to be associated with pathological grade,and ARL4C high-expression patients have unfavorable outcomes.ARL4C may serve as a prognostic factor in patients with glioma and new potential therapeutic target.