肝细胞肝癌上皮型钙黏素基因表达和启动子甲基化研究

Expression of E-cadherin gene and methylation of promoter in hepatocellular carcinoma

目的 探讨上皮型钙黏素（E—cad）基因表达和启动子CpG岛甲基化与肝细胞肝癌（HCC）的关系。方法 用甲基化特异性PCR技术检测36例HCC肿瘤组织及其癌旁非肿瘤组织中，E—cad基因启动子CpG岛甲基化状况，E—cad mRNA表达用RT—PCR技术检测。结果 癌旁组织中E—cad mRNA表达水平显著高于肿瘤组织（P〈0．001），Ⅲ～Ⅳ期肿瘤组织中的表达水平显著低于Ⅰ～Ⅱ期肿瘤（P=0．025），较大肿瘤（〉5cm）组织中的表达水平显著低于较小肿瘤（P=0．035），包膜完整的肿瘤组织中E—cad mRNA表达水平显著高于包膜不完整的肿瘤（P=0．001）;E—cad基因在HCC肿瘤组织中的甲基化率显著高于癌旁组织（P=0．035），在包膜完整的肿瘤中的甲基化率显著低于包膜不完整的肿瘤（P=0．015）；E—cad甲基化阳性的肿瘤组织中，其mRNA表达水平显著低于E-cad非甲基化阳性的肿瘤（P〈0．000）。结论E—cad基因表达下降可能与HCC进展相关，其启动子甲基化是该基因表达下降的重要原因之一。

Objective To investigate the relationships between the expression of E-cadherin （E-cad） gene and the methylation of promoter CpG islands in hepatocellular carcinoma （HCC）. Methods Specimens of tumor tissue and corresponding adjacent liver tissue were collected from 36 cases of hepatocellular carcinoma （HCC）. The expression of E-cad mRNA was detected with RT-PCR technique, and the methylation of CpG islands for E-cad gene was determined with methylation-special PCR both in tumor tissues and adjacent normal liver tissues. Results The levels of E-cad mRNA expression were significantly lower in the HCC tumor tissues than those in corresponding adjacent tissues （P〈0. 001）. E-cad mRNA expression was lower in stage Ⅲ-Ⅳ cases than that in stage Ⅰ-Ⅱ cases （P=0. 025）; lower in tumors 〉5 cm in diameter with that in smaller tumors （P= 0. 035）; lower in well-encapsulated tumors than that in the poor-encapsulated tumors （P=0. 001）. The frequency of methylation of CpG islands for E-cad gene was higher in the HCC tumor tissues than that in the corresponding non-tumor tissues （P=0.035）; and lower in well-encapsulated tumors than that in the poorencapsulated tumors tissues （P=0. 015）. The level of E-cad mRNA expression was significantly lower in the tumors with E- cad methylation than that in the tumors with E-cad non-methylation （P〈0. 001）. Conclusion Decreased E-cad mRNA expression may be involved in the pathogenesis of HCC,which is associated with aberrant methylation of E-cad gene.