肝细胞癌上皮型钙粘素基因甲基化及其临床特征分析

Research on the Relationship between Methylation of E-cadherin and the Clinicopathological Features of Hepatocellular Carcinoma

目的:探讨上皮型钙粘素基因启动子CpG岛甲基化与肝细胞癌(HCC)及其临床病理特征的关系。方法:用甲基化特异性PCR技术检测53例HCC肿瘤组织及其癌旁非肿瘤组织和15例肝海绵状血管瘤周围正常肝组织中,上皮型钙粘素基因启动子CpG岛甲基化状况。结果:上皮型钙粘素基因在HCC肿瘤组织中的甲基化率显著高于癌旁非肿瘤组织(P=0.007,P<0.01),显著高于正常肝组织(P=0.006,P<0.01),在Ⅲ～Ⅳ期肿瘤中的甲基化率显著高于Ⅰ～Ⅱ期肿瘤(P=0.037,P<0.05),在包膜完整的肿瘤中甲基化率显著高于包膜不完整的肿瘤(P=0.043,P<0.05),在HBV阳性的肿瘤组织中甲基化率显著高于HBV阴性的肿瘤组织(P=0.024,P<0.05),在不同大小的肿瘤之间、单个结节与多个结节的肿瘤之间甲基化率的差异均无显著性。结论:上皮型钙粘素基因启动子CpG岛甲基化可能参与肝细胞的癌性转变。

Objective： To study the relationship between methylation of CpG islands in the E-cadherin （E-cad） promoter and clinieopathologic features of hepatocellular carcinoma （HCC）. Methods： The methylation status of CpG islands was studied using Methylation-Speeifie PCR for the E-cad gene in tumor tissues and corresponding normal tissue from 53 HCC patients and 15 cases with paraneoplastic tissues of hepatic sponginess hemangioma. Results： The frequency of methylation of CpG islands in the E-cad gene was significantly higher among the HCC tumor tissues as compared to the correspond- ing normal tissues （P=-0.007, P〈0.01）, and the paraneoplastic liver tissues （P=0.006, P〈0：01）. The frequency of methylation of CpG islands in the E-cad gene was significantly higher in stage Ⅲ-Ⅳ cases as compared to the stageⅠ-Ⅱ eases （P=-0.037, P〈0.05）, and in well-encapsulated tumors compared to poorly-encapsulated tumors （P=0.1M3, P〈0.05）, and in tumor tissues positive for Hepatitis B virus （HBV） compared to tumors negative for HBV （P=-0.024, P〈0.05）. Differences in the frequency of methylation of CpG islands irl the E-cad gene between large tumors （diameter〉5cm） and small tumors （diam- eter≤5cm） and between tumors with a single nodule and multiple nodules were not statistically significant. Conclusion： Methylation of CpG islands for the E-cadherin gene maybe involved in the pathogenesis of HCC.