MGMT 基因在脑胶质瘤组织中表达变化、突变及功能的生物信息学分析.

Bioinformatics analysis of MGMT gene expression, mutation and biological function in gliomas.

Objective To investigate the expression mutation and biological function of 0 6 -methylguanine-DNA methyltransferase ( MGMT) gene in glioma tissues through bioinformatics analysis. Methods The expression level of MGMT gene in glioma tissues was searched in the cancer genome atlas ( TCGA) database. The glioma patients included in the TCGA were divided into the high expression and low expression groups according to the median expression level of MGMT gene. The MGMT gene mutation status in TCGA database was examined by cBioportal. The protein interaction network between MGMT gene and its correlated proteins was constructed by STRING databases and online analysis function. Gene ontology ( OG) was used for biological function enrichment of MGMT and its correlated gene in the protein interaction network. MGMT-related pathway was analyzed by Kyoto Encyclopedia of Genes and Genomes ( KEGG). Results MGMT relative expression level was up-regulated in the tumor tissues compared with that of the normal brain tissues, without statistical difference ( P > 0. 05). The overall survival ( HR = 1. 50, P < 0. 05) and progression free survival ( HR = 1. 50, P < 0. 05) of patients with high MGMT gene expression were significantly lower than those of the patients with low MGMT gene expression. The mutation rate of MGMT gene was 2. 8%, and the mutation spectrum was mainly C >A, C > G, and C > T. There were 21 interacting proteins in the MGMT protein network. The average degree of interaction, aggregation index were 9. 9 and 0. 78, respectively, with statistical difference ( P < 0. 05), which indicated significant proteins enrichment. The biological functions of MGMT gene were mainly enriched in DAN repair, cell response to DNA damage, damaged DNA binding and universal transcription initiation factor binding of RNA polymerase II. MGMT-related signaling pathways were mainly enriched in platinum-based chemotherapeutic drug resistance, cancer signaling pathways, nervous system tumors and DNA mismatch repair. Conclusions MGMT gene is mainly related to DNA mismatch repair, and is up-regulated in glioma. Its high expression is associated with poor prognosis of patients. MGMT gene can be used as a molecular marker of prognosis in glioma. [ABSTRACT FROM AUTHOR]

目的 采用生物信息学方法探讨O6-甲基鸟嘌呤-DNA甲基转移酶 (MGMT) 基因在脑胶质瘤组织中的表达、突变及生物学功能。方法 在癌症基因图谱 (TCGA) 数据库中检索MGMT基因在脑胶质瘤组织中的表达水平;根据 TCGA 数据库中MGMT基因在肿瘤组织中表达的中位数,将患者分为高低表达组,比较两组患者总生存和无疾病进展生存是否存在差异。采用c Bioportal 对 TCGA 数据库中MGMT基因突变情况进行分析。在STRING数据库中构建 MGMT 及其相关基因的蛋白相互作用网络,采用基因本体论 (GO) 对网络中的相关基因进行生物学功能分析,采用京都基因百科全书 (KEGG) 对MGMT基因进行相关信号通路分析。结果 脑胶质瘤组织中MGMT基因表达较正常脑组织上调,但差异无统计学意义(P> 0. 05)。MGMT基因高表达组患者总生存时间 (HR=1. 50,P<0. 05)和无疾病进展生存时间 (HR=1. 50,P <0. 05) 均低于低表达组。MGMT基因突变率为2. 8%,突变谱主要为C> A、C> G、C> T突变。MGMT蛋白网络中相互作用的蛋白有21个,平均相互作用度为9. 9,聚集指数为0. 78,蛋白间富集显著 (P <0. 05)。MGMT基因的生物学功能主要富集于DAN修复、细胞对DNA损伤的反应、受损的DNA结合以及RNA聚合酶Ⅱ转录起始因子结合等,MGMT相关信号通路主要富集于铂类化疗药物耐药、癌症信号通路、神经系统肿瘤和DNA错配修复等。结论 MGMT基因主要与DNA错配修复有关,在脑胶质瘤中表达上调,其高表达与患者预后不良相关,可作为脑胶质瘤预后的分子标志物。 [ABSTRACT FROM AUTHOR]