胶质瘤中DIRAS家族GTP酶3的表达及其预后预测价值  

Expression of DIRAS3 in glioma and its prognostic value

作　　者：丁辉 陈申波 羊良旺 吴然 叶富跃 杨堃 DING Hui;CHEN Shengbo;YANG Liangwang;WU Ran;YE Fuyue;YANG Kun(Department of Neurosurgery,First Affiliated Hospital of Hainan Medical University,Haikou,Hainan 570102,China)

机构地区：[1]海南医科大学第一附属医院神经外科,海南海口570102

出　　处：《中华神经外科疾病研究杂志》2025年第1期5-12,共8页Chinese Journal of Neurosurgical Disease Research

基　　金：国家自然科学基金(82060456);海南省金融科技项目(ZDYF2022SHFZ088)。

摘　　要：目的探讨DIRAS家族GTP酶3(DIRAS3)在胶质瘤中的表达及其预后预测价值。方法使用阿拉巴马大学伯明翰分校癌症数据分析门户(The University of ALabama at Birmingham Cancer data analysis Portal,UALCAN)、基因表达谱交互分析2.0(Gene Expression Profiling Interactive Analys,GEPIA 2.0)和人类蛋白质图谱(Human Protein Atlas,HPA)数据库评估DIRAS3在癌症基因组图谱计划(The Cancer Genome Atlas Program,TCGA)数据库中低级别胶质瘤(low-grade glioma,LGG)和胶质母细胞瘤(glioblastoma,GBM)中的表达及对临床预后的预测价值,并利用反转录实时定量PCR(real-time quantitative reverse tranion PCR,qRT-PCR)和蛋白印迹(western blotting,WB)验证DIRAS3在人星型胶质细胞和胶质瘤细胞中的表达。基于cBioPortal数据库分析GBM中与DIRAS3正相关的基因,利用STRING数据库进行聚类,选择包含DIRAS3的Cluster进行基因本体论(gene ontology,GO)和京都基因和基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)分析。利用泛癌药物敏感性的综合分析(comprehensive analysis of drug sensitivity in pancancer,CADSP)数据库进行药物敏感性分析。结果DIRAS3在胶质瘤中高表达并与世界卫生组织(World Health Organization,WHO)分级、异柠檬酸脱氢酶(isocitrate dehydrogenase,IDH)状态、1p/19q共缺失状态、年龄以及较差的预后相关。此外,DIRAS3被预测参与细胞运动正向调节、焦点粘附、血管发育,以及癌症中的转录失调,并对多种抗肿瘤药物敏感。结论DIRAS3在胶质瘤中具有致癌作用,是一种新的、预后相关的候选基因,并且是胶质瘤的潜在诊断标志物和有希望的治疗靶点。Objective To investigate the expression of DIRAS family GTPase 3(DIRAS3)in glioma and its prognostic value.Methods UALCAN,GEPIA 2.0,and HPA databases were used to evaluate and verify the expression of DIRAS3 in human astrocytes and glioma cells.Genes positively related to clinical prognostic value of DIRAS3 in TCGA-LGG&GBM were analyzed based on the cBioPortal database,and a Cluster containing DIRAS3 was selected for GO and KEGG analysis using the STRING database.The qRT-PCR and WB were used on DIRAS3 in GBM.Drug sensitivity was analyzed by the CADSP database.Results DIRAS3 expression was highly correlated with WHO grade,Isocitrate Dehydrogenase(IDH)status,1p/19q co-deletion status,age,and poor prognosis.In addition,DIRAS3 was involved in the positive regulation of cell movement,focal adhesion,vascular development,and transcriptional dysregulation in cancer,and was sensitive to multiple anti-tumor drugs.Conclusions As it has a carcinogenic effect in gliomas,DIRAS3 is a novel,prognostic relevant candidate gene which can serve as both a potential diagnostic marker and a promising therapeutic target for gliomas.

关 键 词：胶质瘤 DIRAS家族GTP酶3 药物敏感性 治疗靶点 

分 类 号：R739.41[医药卫生—肿瘤]