摘要
目的通过检测肝细胞癌中p14ARF基因启动子甲基化状态与蛋白表达的关系,探讨p14ARF基因启动子甲基化与肝细胞癌的关系。方法通过甲基化特异性PCR(MSP)方法及免疫组化(IHC)法分别检测50例肝细胞癌组织和癌旁组织中p14ARF基因启动子甲基化状态和蛋白表达水平。结果癌组织及癌旁组织中p14ARF基因启动子甲基化阳性率分别为28%(14/50)和4%(2/50)(P<0.01)。癌与癌旁组织p14ARF蛋白表达差异极显著(P<0.01)。p14ARF基因启动子甲基化和蛋白表达与临床分期、门脉癌栓、术后复发、肝外转移、肿瘤大小、肿瘤个数及血清AFP值无关,而在肿瘤分化程度上p14ARF蛋白表达有显著差异,p14ARF基因启动子甲基化则无差异。p14ARF基因启动子甲基化与蛋白表达呈负相关。结论启动子区甲基化是p14ARF基因失活的重要机制。p14ARF启动子区异常甲基化可能参与了肝癌的发生、发展,在肝癌的进展中起重要作用。
Objective To investigate promoter methylation status and protein expression of p14^ARF gene in hepatocellular carcinoma （HCC）, and to evaluate the role of p14^ARF promoter methylation in carcinogenesis of HCC. Methods Promoter methylation status and protein expression of p14^ARF gene were analyzed in 50 cases of HCC by methylation specific polymerase chain reaction （MSP） and immunohistochemestry （IHC）, respectively. Results The positive rate of p14^ARF promoter methylation in tumor and normal tissues adjacent to cancer was 28.0% （14/50） and 4.0% （2/50）, respectively （ P 〈 0.01 ）. The positive rate of p14^ARF protein in tumor tissues was significantly lower than that in normal tissues adjacent to cancer （ P 〈 0.01）. Promoter methylation and protein expression of p14^ARF was not correlated with the the clinical stage, tumor thrombus in portal vein, recurrence of tumor, presence of extrabepatic metastasis, diameter of tumor, number of tumor, and level of serum alpha-fetoprotein （AFP）. The protein expression of p14^ARF in the HCC tissue was significantly correlated with the differentiation of tumor. On the contrary, p14^ARF promoter methylation was not. Promoter methylation and protein expression of p14^ARF gene showed a significantly negative correlation （γ = -0.493, P 〈 0.01 ）. Conclusion Promoter methylation is a crucial mechanism of inactivation of p14^ARF gene. Promoter methylation of p14^ARF gene might be involved in carcinogenesis and development of HCC, and play an important role in progress of HCC.
出处
《诊断病理学杂志》
CSCD
2008年第3期202-205,共4页
Chinese Journal of Diagnostic Pathology
基金
广西卫生厅自筹经费科研课题资助项目(Z2005155)
关键词
肝细胞癌
抑癌基因
P14^ARF
甲基化
Hepatocellular carcinoma
Tumor suppressor gene
p14^ARF
Methylation
