基于跨平台整合微阵列法研究多基因联合评估胶质母细胞瘤病人预后的作用

项目名称： 基于跨平台整合微阵列法研究多基因联合评估胶质母细胞瘤病人预后的作用

项目编号： No.81201980

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 别黎

作者单位： 吉林大学

项目金额： 23万元

中文摘要： O6-甲基鸟嘌呤-DNA-甲基转移酶（MGMT）启动子甲基化状态在指导胶质瘤母细胞瘤病人（GBMs）治疗和预后评估中发挥重要作用。但临床应用尚存不足，MGMT启动子发生甲基化的GBMs应用替莫唑胺联合放疗的预后仍有差异；在GBMs的初发和复发肿瘤中MGMT启动子甲基化状态存在转换现象。本课题组前期研究中应用生物信息学技术对TCGA数据库中355例GBM微阵列数据进行跨平台整合分析，结合DNA拷贝数，DNA甲基化状态，mRNA表达筛选评估预后的候选基因，并且发现MGMT启动子甲基化状态转换和GBMs预后相关；拟进一步在冰冻、石蜡标本验证候选基因，建立并验证多基因联合的预后评估模型；研究启动子甲基化状态转换对GBMs预后的影响，应用肿瘤细胞株研究MGMT启动子甲基化状态转换和化疗抵抗的机制。本研究对揭示GBM进展的分子机制、实现GBMs个体化治疗具有重要的理论和现实意义。

中文关键词： 胶质母细胞瘤；O6-甲基鸟嘌呤-DNA甲基转移酶；替莫唑胺；微阵列；预后

英文摘要： O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status play an important role in the treatment and prognostic evaluation of the guidance gliomablastoma patients (GBMs). However, there have inadequacies in the clinical application. MGMT promoter methylation in the GBMs application of temozolomide combined with radiotherapy treatment prognosis are still differences; MGMT promoter methylation status of existence of the conversion phenomena in the primary and recurrent tumors. In the preliminary research, we cross-platform integrate 355 cases of GBM microarray datasets in TCGA database, combined with the DNA copy number, DNA methylation status and mRNA expression of candidate genes screening assessment of prognosis and the impact of MGMT promoter methylation state conversion; The proposed further in frozen and paraffin-embedded specimens to validate the candidate gene, multi-gene combined with the prognostic evaluation model developed and validated; the promoter methylation status of conversion affect the prognosis of GBMs, to research the mechanism of MGMT promoter methylation state conversion and chemotherapy resistance in tumor cell lines. This study reveals the molecular mechanism of GBM progress, GBMs individual treatment have important theoretical and practical significance.

英文关键词： GBM；MGMT；TMZ；Microarray；Prognosis