MGMT甲基化影响替莫唑胺对胶质母细胞瘤疗效的研究  

Effect of Promoter Hypermethylation of DNA Repair Gene O^6-methylguanine DNA Methyltransferase to the Treatment of Temozolomide in Glioblastoma

作　　者：李庆斌[1] 李瑞岩[1] 丛方方 丁美娇 李永利[1] 

机构地区：[1]哈尔滨医科大学第二临床医学院神经外科,黑龙江哈尔滨150086 [2]哈尔滨市儿童医院,黑龙江哈尔滨150010

出　　处：《现代生物医学进展》2012年第8期1471-1475,1494,共6页Progress in Modern Biomedicine

摘　　要：目的:探讨MGMT甲基化如何影响替莫唑胺对胶质母细胞瘤的治疗效果。方法:选取41个胶质母细胞瘤患者(根据相同替莫唑胺化疗方案治疗下临床结局的不同分为两组)的肿瘤组织,采用甲基化特异性聚合酶链反应分析胶质瘤组织中MGMT基因启动子区过甲基化状态,同时采用免疫组织化学法分析胶质瘤组织中MGMT蛋白表达情况。结果:临床结局不佳组中,以MGMT蛋白表达阳性的肿瘤为主(72.2%),而在结局相对良好组中,MGMT蛋白表达的阳性率仅为39.1%;在MGMT蛋白表达阳性的22例胶质母细胞瘤组织中,7例MGMT启动子甲基化,阳性率为31.8%,在MGMGT蛋白表达阴性的19例中,14例MGMT启动子甲基化,阳性率为73.7%(P<0.05)。结论:MGMT基因启动子区的甲基化状态与MGMT蛋白的表达相关。MGMT基因启动子过甲基化,MGMT蛋白表达较低;MGMT基因启动子去甲基化,MGMT蛋白表达较高。MGMT启动子过甲基化通过抑制MGMT基因的表达而增加替莫唑胺的疗效。Objective： To investigate the effect of the hypermethylation of MGMT promoter on the treatment of temozolomide to glioblastomas（GBM）.Methods： Tumors were chosen（divided into two groups according to different clinical endings with the same treatment of temozolomide）;Methylation-specific PCR was used to detect the promoter methylation of the MGMT gene and loss of transcription in glioma tissues.MGMT expression was examined by immunohistochemistry method.Results： The majority（72.2%） of tumors＇ MGMT protein expressed positive in the group whose clinical endings are bad,but the positive rate is only 39.1% in the other group whose clinical endings are relatively good.Among the 41 GBM samples,MGMT expressed in 22 samples,in which hypermethylation was in 7（31.7%） cases,while there was no MGMT expression in 19 samples,in which hypermethylation was detected in 14（73.7%） cases.Spearman correlation coefficient was used to analyze the result.The relation was significant（P〈0.05）.Conclusion： The relationship between the aberrant methylation of MGMT gene promoter and the expression of MGMT in glioma is significant.The promoter hypermethylation of MGMT can elevate the sensitive of temozolomide through inhibiting the expression of MGMT gene.

关 键 词：胶质母细胞瘤 MGMT(O6-甲基鸟嘌呤DNA甲基转移酶) 替莫唑胺 甲基化 免疫组织化学 

分 类 号：R739.4[医药卫生—肿瘤]