原发性肝癌p14ARF基因CpG岛甲基化研究  

5′CpG methylation of p14ARF gene in hepatocellular carcinoma

作　　者：阮新贤[1] 王少平[2] 陈孝平[2] 任培土[1] 

机构地区：[1]绍兴市人民医院普外科,312000 [2]华中科技大学同济医院肝脏中心

出　　处：《中华普通外科杂志》2007年第11期848-850,共3页Chinese Journal of General Surgery

摘　　要：目的探讨p14ARF基因启动子区CpG岛甲基化与原发性肝细胞肝癌发生、发展的关系。方法采用逆转录-聚合酶链式反应（RT-PCR）检测42例原发性肝癌组织及癌旁组织中p14ARFmRNA的表达,同时用甲基化特异PCR（methylation-specific PCR,MSP）方法分析p14ARF基因启动子区域甲基化状况。结果42例肝癌组织有7例呈p14 mRNA的表达,表达率17%。癌旁正常组织均有p14表达。p14mRNA在原发性肝癌组织中明显表达缺失（χ^2=56.62,P〈0.05）;42例原发性肝癌组织中,有19例检测到p14基因启动子的甲基化,甲基化发生率45%。相应癌旁组织未发现甲基化。p14ARF基因在原发性肝癌呈现明显高甲基化（χ^2=22.04,P〈0.05）。在p14mRNA表达的7例肝癌组织中没有检测到p14基因启动子的甲基化,而在p14mRNA表达缺失的35例肝癌组织中。19例p14基因启动子呈现甲基化。肝癌组织中p14ARF基因启动子甲基化与p14mRNA表达缺失明显相关（χ^2=4.66,P〈0.05）。结论在原发性肝癌p14 mRNA明显表达缺失,原发性肝癌p14ARF基因启动子频繁甲基化可能是p14ARF失活的原因之一。Objective To explore the relationship between the methylation at p14ARF locus and the progression of hepatocellular carcinoma （ HCC ）. Methods Reverse-transcription polymerase chain reaction （RT-PCR） assay was used to examine the expression of p14ARF mRNA in 42 HCC samples and corresponding noncancerous tissues. Methylation-specific PCR （MSP） was performed to detect the methylation at p14ARF promoter region in those HCC tissues and matched adjacent noncancerous liver tissues. Results RT-PCR assay revealed p14ARF positive mRNA expression in 7 of 42 （ 17% ） in HCC tissues and all of corresponding noncancerous tissues. Compared to corresponding normal tissues, p14ARF mRNA level was significantly decreased in HCCs tissues （χ^2 = 56. 62, P 〈 0. 05 ）. Aberrant promoter methylation of the p14 gene was detected by MSP technique in 19 of 42（45% ） HCC tissues, and there was no methylation found in adjacent noncancerous tissues （ χ^2 = 22. 04 , P 〈 0. 05 ）. In 19 out of 35 HCC tissues with negative p14ARF mRNA expression there was hypermethylation at p14ARF promoter region, whereas, no methylation of p14 was detected in 7 HCC tissues with positive p14ARF mRNA expression （χ^2= 4. 66, P 〈 0. 05 ）. Conclusion p14ARF mRNA expression was significantly decreased in HCC tissues. Frequent hypermethylation at p14ARF locus might contribute to the loss of expression of p14ARF gene in HCC. The hypermethylation at p14ARF locus may play a role in the pathogenesis of HCC.

关 键 词：癌 肝细胞 基因表达 P14ARF 甲基化 

分 类 号：R686[医药卫生—骨科学]