DKK-3和WIF-1基因启动子甲基化状态与肝细胞癌的关系研究

目的探讨DKK-3和WIF-1基因启动子甲基化状态与肝细胞癌发生的相关性。方法应用甲基化特异性聚合酶链反应检测33例肝细胞癌及相应的癌旁组织和20例正常对照肝组织中DKK-3和WIF-1基因启动子甲基化状态。分析上述组织中两种基因甲基化状态与临床资料的关系。结果DKK-3和WIF-1基因在癌组织中甲基化率明显高于癌旁组织和正常组织（P〈0．05，P〈0．05），而癌旁组织和正常组织中DKK-3和WIF-1基因甲基化率相比无明显差异；癌组织中DKK-3基因甲基化与临床资料中年龄及肝硬化有关；癌组织中WIF-1基因甲基化与临床资料中乙肝表面抗原、肝硬化有关。结论DKK-3和WIF-1基因启动子甲基化与HCC的发生相关；DKK-3和WIF-1基因致肝细胞癌的发生机制可能与肝硬化致肝细胞癌的发生机制不尽相同，两者是否有相互作用尚不清楚。

Promoter methylation and mRNA expression of DKK-3 gene in hepatocellular carcinoma

Objective To investigate the promoter methylation status of DKK-3 and WIF-1 gene in hepatocellular carcinoma. Methods Methylation status of DKK-3 and WlF-1 gene promoter were detected by methy fation specific PCR in 33 hepatocellular carcinomas and adjacent non-cancerous tissues, 20 normal liver tissue as control. The relationship between methylation and clinical data of the two genes was analyzed. Results Methylation of DKK-3 and WlF-1 genes in hepatocel- lular carcinoma increased significantly compared with adjacent trol tissues （ X^2 = 7.79, P 〈 0.05 ; X^2 = 4.89, P 〈 0.05） and there was no significant difference in methylation between adjacent non-cancerous tissues and normal control tissues; In HCC tissues, significant differences of the DKK-3 promoter methylation were observed in ages and cirrhosis; significant differences of the WIF-1 promoter methylation were observed in HBsAg and cirrhosis. Conclusion The aberrant promoted methylations of DKK-3 and WIF-1 genes are both high related to hepatocarcinogenesis. The hepatocarcinogenesis induced by DKK-3 and WIF-1 may be different from that induced by cirrhosis, and it is unknown whether there is any interaction between the twofactots.