获得持续病毒学应答的患者与丙型肝炎病毒感染患者之间肝细胞癌分子改变的差异。

Differences in molecular alterations of hepatocellular carcinoma between patients with a sustained virological response and those with hepatitis C virus infection.

作者信息

Hayashi Takehiro, Tamori Akihiro, Nishikawa Manabu, Morikawa Hiroyasu, Enomoto Masaru, Sakaguchi Hiroki, Habu Daiki, Kawada Norifumi, Kubo Shoji, Nishiguchi Shuhei, Shiomi Susumu

机构信息

Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.

出版信息

Liver Int. 2009 Jan;29(1):126-32. doi: 10.1111/j.1478-3231.2008.01772.x. Epub 2008 May 19.

DOI:10.1111/j.1478-3231.2008.01772.x

PMID:18492017

Abstract

BACKGROUND/AIMS: The mechanism of hepatocarcinogenesis remains unclear in patients in whom hepatitis C virus (HCV) disappears after interferon (IFN) therapy. We compared molecular alterations in hepatocellular carcinoma (HCC) between patients with a sustained virological response (SVR) to IFN and patients with HCV.

METHODS

The study group comprised 44 patients with HCV and 13 patients with SVR. One patient in the SVR group had two tumour nodules, both of which were examined. Mitochondrial DNA (mtDNA) mutations in displacement-loop lesions were directly sequenced. Mutation of the TP53 gene was examined by direct sequencing. The methylation status of p16, p15, p14, RB and PTEN genes was evaluated by a methylation-specific polymerase chain reaction.

RESULTS

The average number of mtDNA mutations was 4.2 in 44 HCCs with HCV and 2.0 in 14 HCCs with SVR (P=0.0021). mtDNA mutation was less frequently detected in HCCs from patients with SVR than in patients with HCV. TP53 mutations were detected in 12 (27%) of 44 HCCs with HCV and 2 (14%) of 14 SVR-HCCs. Hypermethylation of the p16, p15, p14, RB and PTEN promoters was, respectively, detected in 34, 13, 8, 12 and 11 of 44 HCCs from patients with HCV and 14, 0, 0, 2 and 2 of 14 HCCs from patients with SVR (P=0.049, 0.021, 0.085, 0.322 and 0.402). Hypermethylation of p16 was one of the most important alterations in SVR-HCC.

CONCLUSIONS

Molecular alterations in hepatocarcinogenesis of patients with SVR-HCC were different from those of patients with continuous HCV infection.

摘要

背景/目的：在接受干扰素（IFN）治疗后丙型肝炎病毒（HCV）消失的患者中，肝癌发生的机制仍不清楚。我们比较了实现病毒学持续应答（SVR）的患者与HCV患者肝细胞癌（HCC）中的分子改变。

方法

研究组包括44例HCV患者和13例SVR患者。SVR组中有1例患者有两个肿瘤结节，均进行了检查。对置换环区域的线粒体DNA（mtDNA）突变进行直接测序。通过直接测序检测TP53基因的突变。通过甲基化特异性聚合酶链反应评估p16、p15、p14、RB和PTEN基因的甲基化状态。

结果

44例HCV相关HCC中mtDNA突变的平均数为4.2，14例SVR相关HCC中为2.0（P = 0.0021）。与HCV患者相比，SVR患者的HCC中mtDNA突变的检出频率较低。44例HCV相关HCC中有12例（27%）检测到TP53突变，14例SVR相关HCC中有2例（14%）检测到TP53突变。在44例HCV患者的HCC中，分别有34例、13例、8例、12例和11例检测到p16、p15、p14、RB和PTEN启动子的高甲基化，在14例SVR患者的HCC中，分别有14例、0例、0例、2例和2例检测到p16、p15、p14、RB和PTEN启动子的高甲基化（P = 0.049、0.021、0.085、0.322和0.402）。p16的高甲基化是SVR相关HCC中最重要的改变之一。