p16（INK4A）基因甲基化从正常肝脏到非肿瘤性肝脏及肝细胞癌的进展：一项运用定量PCR分析的评估

Progression of hypermethylation of the p16(INK4A) gene from normal liver to nontumorous liver and hepatocellular carcinoma: an evaluation using quantitative PCR analysis.

作者信息

Kurita So, Ohkoshi Shogo, Yano Masahiko, Yamazaki Kazuhide, Suzuki Kenta, Aoki Yo-hei, Matsuda Yasunobu, Wakai Toshifumi, Shirai Yoshio, Ichida Takafumi, Aoyagi Yutaka

机构信息

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences of Niigata University, 1-754, Asahimachi-Dori, Niigata-city, 951-8122, Japan.

出版信息

Dig Dis Sci. 2009 Jan;54(1):80-8. doi: 10.1007/s10620-008-0611-5. Epub 2008 Nov 19.

DOI:10.1007/s10620-008-0611-5

PMID:19016326

Abstract

The aim of this study was to determine to what extent hypermethylation of the p16(INK4A) (p16) gene promoter is increased in nontumorous liver tissues compared with in normal liver, using two quantitative methylation-specific polymerase chain reaction (MS-PCR) methods and a bisulfite sequencing method. Methylation of the p16 gene was detected more frequently in nontumorous liver than in normal liver using the TaqMan PCR method. Methylation indices also were significantly higher in nontumorous than in normal liver. However, the bisulfite sequencing method did not detect significantly more methylation of the p16 gene in nontumorous than normal liver, nor was there a significant difference in the level of p16 mRNA. There may be a greater proportion of cells which contain methylated p16 in nontumorous than in normal liver. However, the difference was so small that the functional relevance to hepatocarcinogenesis remains elusive.

摘要

本研究的目的是使用两种定量甲基化特异性聚合酶链反应（MS-PCR）方法和亚硫酸氢盐测序法，确定与正常肝脏相比，非肿瘤性肝组织中p16（INK4A）（p16）基因启动子的高甲基化增加的程度。使用TaqMan PCR方法检测到非肿瘤性肝脏中p16基因的甲基化比正常肝脏中更频繁。非肿瘤性肝脏中的甲基化指数也显著高于正常肝脏。然而，亚硫酸氢盐测序法未检测到非肿瘤性肝脏中p16基因的甲基化比正常肝脏显著更多，p16 mRNA水平也没有显著差异。非肿瘤性肝脏中可能含有甲基化p16的细胞比例比正常肝脏中更大。然而，差异非常小，与肝癌发生的功能相关性仍然难以捉摸。