乙型肝炎病毒既往感染在日本HBs抗原阴性及抗-HCV阴性肝细胞癌患者中的作用：病因学及分子生物学研究

The role of previous infection of hepatitis B virus in Hbs antigen negative and anti-HCV negative Japanese patients with hepatocellular carcinoma: etiological and molecular biological study.

作者信息

Matsuzaki Y, Sato M, Saito Y, Karube M, Doy M, Shoda J, Abei M, Tanaka N, Hadama T, Kinoshita M

机构信息

Dept. of Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.

出版信息

J Exp Clin Cancer Res. 1999 Sep;18(3):379-89.

PMID:10606185

Abstract

The aim of this study is to elucidate the important role of the previous infection of HBV, and the relations among HBV genome integration and p53 gene mutation, telomerase activity and genetic instability in liver tissue with HBsAg-negative (NB) and anti-HCV negative (NC) hepatocellular carcinoma (HCC). We examined the backgrounds of 34 NB and NC (NBNC) Japanese patients with chronic liver disease (CLD) patients not associated with HCC and 26 NBNC CLD patients with HCC. HBV genome integration into host cell genome, p53 gene mutation telomerase activity and genetic instability were examined in 6 with NBNC HCC (NBNC-HCC) tumorous tissue (T) and non-tumorous tissues (NT). In the NBNC group, HBV-related antibody positive patients with HCC are significantly more than the patients without HCC. Moreover, concerning the stage of the coexisted liver diseases, in NBNC CLD, LC patients with HCC is 19 of 26 (73.1%) , on the other hand, LC patients without HCC is 16 of 34 (47.1%). LC patients with HCC group is significantly more than that without HCC. Three (50%) of 6 in T and 3 cases (50% ) in NT were found to integrated genome of HBV. p53 gene mutation was observed in 3 (50%) of T. Concerning the telomerase activity, 3 of 6 cases (50%) in T and 1 case in NT was recognized. There was no genetic instability (LOH or RER) of D2S123, D3S1067 and TP 53 in T and NT. Finally in T of NBNC HCC cases, TTVDNA was detected in 3 of 5. Even in the HBsAg-negative and anti-HCV negative HCC cases, CLD coexisting with LC, previous HBV infection and HBVDNA integration were observed. There were a few cases with HBVDNA integration, p53 gene mutation, telomerase activity and genetic instability, simultaneously in HCC tissue, and in some cases, the coexistence with TTVDNA were concurrently confirmed. It is speculated that the important role of the previous infection of HBV may have also been proposed for HCC oncogentic progression in NBNC CLD [corrected].

摘要

本研究旨在阐明乙肝病毒（HBV）既往感染的重要作用，以及HBV基因组整合与p53基因突变、端粒酶活性和遗传不稳定性在乙肝表面抗原阴性（NB）和抗丙肝病毒阴性（NC）肝细胞癌（HCC）肝组织中的关系。我们研究了34例不伴有HCC的慢性肝病（CLD）日本患者（NB和NC，即NBNC）以及26例伴有HCC的NBNC CLD患者的背景情况。对6例NBNC HCC（NBNC-HCC）患者的肿瘤组织（T）和非肿瘤组织（NT）检测了HBV基因组整合入宿主细胞基因组、p53基因突变、端粒酶活性和遗传不稳定性。在NBNC组中，HBV相关抗体阳性的HCC患者显著多于无HCC的患者。此外，关于并存肝病的阶段，在NBNC CLD中，伴有HCC的肝硬化（LC）患者在26例中有19例（73.1%），而无HCC的LC患者在34例中有16例（47.1%）。伴有HCC的LC患者组显著多于无HCC的患者组。6例中的3例（50%）T组织和3例（50%）NT组织中发现有HBV基因组整合。3例（50%）T组织中观察到p53基因突变。关于端粒酶活性，6例中的3例（50%）T组织和1例NT组织中检测到。T组织和NT组织中未发现D2S123、D3S1067和TP 53的遗传不稳定性（杂合性缺失或微卫星序列改变）。最后，在NBNC HCC病例的T组织中，5例中有3例检测到TTVDNA。即使在HBsAg阴性和抗HCV阴性的HCC病例中，也观察到与LC并存的CLD、既往HBV感染和HBVDNA整合。在HCC组织中，有少数病例同时存在HBVDNA整合、p53基因突变、端粒酶活性和遗传不稳定性，在某些情况下，还同时证实与TTVDNA并存。推测既往HBV感染的重要作用可能也与NBNC CLD中HCC的致癌进展有关[已校正] 。