宫颈癌组织中DAPK基因启动子甲基化的研究

背景与目的:已有研究表明DNA异常甲基化在肿瘤的发生、发展中发挥了重要作用.本研究旨在探讨宫颈癌组织中DAPK(death-associated protein kinase)启动子甲基化与基因失活的关系.方法:应用甲基化特异性PCR (methylation-specific PCR,MSP)技术检测52例宫颈癌、60例宫颈上皮内瘤样病变(cervical intraepithelial neoplasia,CIN)和20例正常宫颈鳞状上皮DAPK启动子甲基化状况,应用免疫组化方法检测其蛋白表达;分析DAPK启动子甲基化和基因失活与宫颈癌临床病理因素之间的关系.结果:正常宫颈组织不存在DAPK基因启动子CpG岛甲基化,而CIN和宫颈癌中的DAPK甲基化率分别为18.3%(11/60)、65.4%(34/52),三者之间的差异有统计学意义(P<0.05).宫颈鳞癌的DAPK甲基化率明显高于腺癌(分别为80.0%和16.7%),其差异有统计学意义(P<0.001).DAPK启动子甲基化和DAPK蛋白表达之间呈负相关(r=-0.849,P<0.001).结论:DAPK启动子CpG岛甲基化可导致基因失活,并可能参与宫颈癌的发生.

Promoter methylation of DAPK gene in cervical carcinoma

BACKGROUND & OBJECTIVE: Aberrant DNA methylation plays important roles during multistage carcinogenesis in various human organs. This study was to explore the relationship between the promoter methylation and inactivation of DAPK gene in cervical cancer. METHODS: The promoter methylation of DAPK was investigated with methylation-specific polymerase chain reaction (MSP) in 52 specimens of cervical cancer, 60 specimens of cervical intraepithelial neoplasia (CIN) and 20 specimens of normal cervical squamous epithelial tissues. Its correlation to clinicopathologic features of cervical cancer was analyzed. The protein expression of DAPK was detected by immunohistochemistry. RESULTS: The methylation rate of DAPK gene promoter was significantly higher in cervical cancer tissues than in CIN (65.4% vs. 18.3%, P<0.05); while no methylation of DAPK gene was found in normal cervical tissues. The methylation rate of DAPK gene was significantly higher in cervical squamous cell carcinomas than in adenocarcinomas (80.0% vs. 16.7%, P<0.001). Promoter methylation of DAPK was negatively correlated to its protein expression (r=-0.849, P<0.001). CONCLUSION: The promoter methylation may lead to inactivation of DAPK gene, and may be related with tumorigenesis of cervical cancer.