摘要
目的探讨抑癌基因E-cadherin基因启动子区CpG岛甲基化与人原发性肝癌(简称肝癌)发生、发展的关系,及其在肝癌早期诊断中的意义。方法用巢式甲基化特异性PCR对34例肝癌患者的癌组织、距离癌灶边缘>3 cm的远癌组织及10例未发生肝癌的肝硬变患者的肝硬变组织中E-cadherin基因启动子区CpG岛的甲基化状态进行检测。结果 E-cadherin基因启动子区CpG岛甲基化阳性率,在34例肝癌组织中为61.76%(21/34),明显高于远癌组织中的29.41%(10/34),P<0.05;在10例无肝癌的肝硬变组织中为50.00%(5/10),与肝癌组织和远癌组织比较差异均无统计学意义(P>0.05);在4例正常肝组织中均为甲基化阴性。联合检测癌组织E-cadherin基因CpG岛甲基化与血清甲胎蛋白两种分子标志物,肝癌的检出率可达82.35%。结论抑癌基因E-cadherin启动子区CpG岛甲基化可能在肝癌的发生、发展中起到重要作用,并且可能是早期事件,其在肝癌的临床诊断及治疗中的意义值得进一步深入研究。
Objective To explore the relationship between aberrant promoter CpG islands methylation status of E-cadherin gene and hepatocarcinogenesis,and to assess its significance in clinical early diagnosis of hepatocellular carcinoma（HCC）.Methods Surgically resected specimens,among which cancerous and corresponding noncancerous liver tissues from 34 HCC patients,10 liver cirrhosis from patients without HCC and normal liver tissues from 4 accidental deaths,were collected in West China Hospital.Breast cancer cell line MDA-MB-435 with promoter CpG islands hypermethylation of E-cadherin as positive control was gained from the Cell Bank of Chinese Academy of Sciences in Shanghai.The methylation status of promoter CpG island of E-cadherin gene was detected by nested methylation-specific polymerase chain reaction（nested-MSP）.Results E-cadherin gene promoter CpG islands hypermethylation was found in 61.76%（21/34） of cancerous tissues,in 29.41%（10/34） of non-cancereous tissues from the 34 HCC patients and in 50.00%（5/10） liver cirrhosis from patients without HCC.None of the 4 normal liver samples were detected E-cadherin mehylation positive.Moreover,the methylation of E-cadherin gene was significantly more frequent in 34 cancerous than that in corresponding non-cancerous liver tissues（P0.05）,which had no significant difference between the 10 cirrhotic samples and cancerous or non-cancerous liver tissues（P0.05）.In 34 cancerous samples,with the combination of both biomarkers of E-cadherin methylation and AFP400（serum AFP level at a cutoff of 400 μg/L）,the diagnostic sensitivity of HCC increased to 82.35%.Conclusions The aberrant promo-ter methylation of E-cadherin gene may play a vital role in the development and progression of HCC.Moreover,it might be an early event in hepatocarcinogensis.It is of high value to make further study to confirm the significance of E-cadherin gene methylation in clinical diagnosis and therapy.
出处
《中国普外基础与临床杂志》
CAS
2011年第5期514-519,共6页
Chinese Journal of Bases and Clinics In General Surgery
基金
四川省科技厅项目(项目编号:2008SZ0028)~~
