中国北方人群p14^(ARF)启动子甲基化与原发性肝癌的临床相关性

p14^(ARF) promoter methylation and its clinical correlation in primary liver cancer in the population of North China

目的通过对中国北方人群原发性肝癌p14ARF启动子甲基化的分析,探讨p14ARF基因启动子甲基化与原发性肝癌的临床相关性。方法通过甲基化特异性PCR(MSP)方法检测111例原发性肝癌组织和22例癌旁组织中p14ARF基因启动子甲基化状况,然后与肿瘤种类、病因、病理以及肿瘤分期等临床数据进行关联。结果肝细胞癌组织及癌旁组织中p14ARF基因启动子甲基化频率分别为33.7%(29/86)和5.0%(1/20),二者差异有统计学意义(P=0.010)。肝细胞癌p14ARF基因的启动子甲基化频率在不同肿瘤分期显著相关(P=0.027),而与肿瘤细胞分化程度以及是否感染HBV无关,肝内胆管细胞癌p14ARF基因启动子甲基化频率在不同肿瘤分期、有无HBV感染以及不同肿瘤细胞分化程度之间的差异均无统计学意义。结论肝细胞癌中p14ARF基因启动子甲基化可能是p14ARF基因失活并影响TP53功能的方式之一,p14ARF基因启动子甲基化可能与肝细胞癌发生发展相关。

Objective To explore the clinical correlation between p14ARF promoter methylation and primary liver cancer through analysis of p14ARF promoter methylation in primary liver cancer in the population of North China.Methods By the method of methylation specific PCR（MSP）,the detection of p14ARF promoter methylation in 111 cases of primary liver cancer and 22 cases of adjacent non-tumor tissue were carried out,and then correlated with different clinical variables,such as tumor type,tumor stages,differentiation of tumor cell and with or without HBV infection in tumor.Results Significant difference（P=0.010）of p14ARF promoter methylation between hepatocellular carcinomas（HCC） and adjacent non-tumor tissue was found,with the ratio of 33.7%（29/86）in primary liver cancer and 5.0%（1/20）in non-tumor tissue.Higher frequency of p14ARF promoter methylation was identified in HCC with tumor stage of TNM1 compared with tumor stage of more than TNM1（P=0.027）.No correlation was found between p14ARF promoter methylation and differentiation of tumor cell and with or without HBV infection in HCC,as well as between p14ARF promoter methylation and tumor stages,differentiation of tumor cell and with or without HBV infection in intrahepatic cholangiocellular carcinoma（ICC）.Conclusion p14ARF promoter methylation may constitute one of the important mechanism in inactivation of p14ARF gene and maybe involved in the development and progression of HCC.