[宫颈癌中死亡相关蛋白激酶基因的启动子甲基化]

[Promoter methylation of DAPK gene in cervical carcinoma].

作者信息

Zhao Xian-Lan, Meng Zhi-Ying, Qiao Yu-Huan, Zhang Hui-Li

机构信息

Department of Obstetrics and Gynecology,The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, 450052, PR China.

出版信息

Ai Zheng. 2008 Sep;27(9):919-23.

PMID:18799028

Abstract

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.

摘要

背景与目的

异常DNA甲基化在人体多个器官的多阶段癌变过程中发挥重要作用。本研究旨在探讨宫颈癌中DAPK基因启动子甲基化与失活之间的关系。

方法

采用甲基化特异性聚合酶链反应（MSP）检测52例宫颈癌标本、60例宫颈上皮内瘤变（CIN）标本和20例正常宫颈鳞状上皮组织中DAPK的启动子甲基化情况。分析其与宫颈癌临床病理特征的相关性。采用免疫组织化学法检测DAPK的蛋白表达。

结果

宫颈癌组织中DAPK基因启动子的甲基化率显著高于CIN（65.4%对18.3%，P<0.05）；而正常宫颈组织中未发现DAPK基因甲基化。宫颈鳞状细胞癌中DAPK基因的甲基化率显著高于腺癌（80.0%对16.7%，P<0.001）。DAPK的启动子甲基化与其蛋白表达呈负相关（r=-0.849，P<0.001）。