DNA修复基因MGMT启动子区过甲基化在胆管癌中的作用  

Promoter Hypermethylation of DNA Repair Gene MGMT in Cholangiocarcinoma

作　　者：刘小方[1] 孙宪春[1] 张翠生[1] 许政[1] 李绍军[1] 周先亭[1] 孙世杰[1] 

机构地区：[1]青岛大学医学院附属烟台毓璜顶医院肝胆外科,山东烟台264000

出　　处：《中国普外基础与临床杂志》2011年第9期947-951,共5页Chinese Journal of Bases and Clinics In General Surgery

基　　金：山东省自然科学基金资助项目(项目编号:Y2008C82)~~

摘　　要：目的探讨胆管癌组织中6-氧-甲基鸟嘌呤-DNA甲基转移酶(MGMT)基因的甲基化状态及其在胆管癌中的临床意义。方法采用甲基化特异性PCR(MSP)和免疫组织化学法分析胆管癌组织中MGMT基因启动子甲基化状态及MGMT蛋白表达情况,并分析MGMT基因甲基化状态与临床病理特征的关系。结果 36例胆管癌组织中MGMT基因17例(47.2%)为甲基化阳性;MGMT蛋白阳性表达15例,阴性表达21例,21例MGMT蛋白阴性表达的胆管癌中MGMT甲基化阳性14例;15例MGMT蛋白阳性表达中MGMT甲基化阳性仅3例。MGMT蛋白表达与MGMT甲基化状态呈负相关(rs=-0.816,P<0.05)。MGMT基因的甲基化状态与胆管癌患者的肿瘤浸润深度、分化程度及TNM分期有关(P<0.05),但与患者的年龄、性别、病理学类型、淋巴结转移均无关(P>0.05)。结论 MGMT基因启动子过甲基化是胆管癌组织中常见的分子事件,并可能与胆管癌发生有关,MGMT甲基化状态可以作为评价胆管癌恶性程度的一项指标。Objective To explore the clinical significance of promoter hypermethylation of O6-methylguanine-DNA methyltransferase（MGMT） in cholangiocarcinoma.Methods Promoter methylation status of MGMT gene and expression of MGMT protein were detected in cholangiocarcinoma by methylation-specific PCR and immunohistochemical staining,respectively.Results Aberrant methylation of MGMT gene was detected in 17 patients（47.2%）.Twenty-one cases showed negative immunoreactivities.Of 21 patients with negative MGMT expression,14 patients had aberrant methylation of MGMT gene.In 15 patients with positive MGMT expression,aberrant methylation of MGMT gene was only found in three cases.There was a negative correlation between promoter methylation status of MGMT gene and the expression of MGMT protein（r_s=-0.816,P0.05）.Promoter methylation status of MGMT gene was related to depth of invasion,degree of differentiation,and TNM stage（P0.05）,but not to age of patient,gender,pathological type,and lymph node metastasis（P0.05）.Conclusions Hypermethylation of MGMT promoter is a frequency molecular event in cholangiocarcinoma and may be involved in carcinogenesis.Methylation status of MGMT gene may be used to evaluate malignant degree of cholangiocarcinoma.

关 键 词：胆管癌 6-氧-甲基鸟嘌呤-DNA甲基转移酶 甲基化特异性聚合酶链反应 表遗传性 过甲基化 

分 类 号：R735.8[医药卫生—肿瘤]