MGMT基因启动子甲基化与膀胱尿路上皮癌生物学行为关系的研究

Relationship between Aberrant Methylation of MGMT Promoter and Biological Behaviour of Bladder Urothelia Carcinoma

目的 检测膀胱尿路上皮癌组织中O^6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）基因启动子甲基化状态,探讨MGMT甲基化与其蛋白表达水平以及肿瘤生物学行为之间的关系.方法 应用免疫组织化学SP法和甲基化特异性PCR（MSP）分别检测60例膀胱尿路上皮癌及15例正常膀胱黏膜组织中MGMT蛋白表达情况和MGMT基因启动子甲基化状态.结果 膀胱癌组织中MGMT蛋白阳性表达率为35.0 %（21/60）,低于正常膀胱组织（86.7 %,13/15,P〈0.01）.膀胱癌组织中MGMT甲基化阳性率为45.0 %（27/60）,明显高于正常膀胱组织（0.0 %,0/15,P〈0.01）;MGMT启动子甲基化与其蛋白表达呈负相关（r = -0.453,P〈0.01）;并且高级别膀胱癌中MGMT甲基化阳性率（70.6 %,12/17）要比低级别膀胱癌高（34.9 %,15/43）,（P〈0.05）,而MGMT甲基化与膀胱癌临床分期无明显关系.结论 MGMT启动子甲基化可能参与了膀胱尿路上皮癌的发生和肿瘤分化,MGMT启动子甲基化有望成为预判膀胱癌预后的重要标记.

Objective To detect the promoter methylation of O^6-methylguanine-DNA methyltransferase （MGMT） gene in bladder urothelia carcinoma and analyze the relationship between MGMT promoter methylation and MGMT protein expression, and study the biological behavior of bladder cancer. Methods Promoter methylation of MGMT gene was detected by methylation-specific PCR （MSP） in 60 samples of human bladder urothelia carcinoma samples and 15 normal bladder tissue samples. Correlations of aberrant methylation of MGMT Promoter to elinicopathologic parameters were statistically analyzed. Results The positive rate of MGMT protein expression in bladder urothelia carcinoma was 35.0 % （21/60） , which was lower than that in normal bladder tissue （86. 7 %, 13/15 ） （ P 〈0. 01 ） . The positive rate of MGMT promoter methylation in bladder urothelia carcinoma was 45.0 % （27/60） , which was obviously higher than that in normal bladder tissue （0. 0 %, 0/15） （P 〈0. 01 ） . A significant relationship was found between aberrant methylation of MGMT and its protein expression （P 〈 0. 05） . Furthermore, the positive rates of MGMT promoter methylation in high-grade and low-grade urothelia carcinoma were 70. 6 % （12/17） and 34. 9 % （ 15/43 ）, respectively （ P 〈 0. 05 ） . No statistical significance was found between MGMT promoter methylation and clinical stage of bladder cancer. Conclusions MGMT promoter hypermethylation plays an important role in carcinogenesis and differentiation of bladder urothelia carcinoma, which might be a prognostic indicator of bladder urothelia carcinoma.