Akhter Shamim, Liu Huifeng, Prabhu Ramesh, DeLucca Cynthia, Bastian Frank, Garry Robert F, Schwartz Myron, Thung Swan N, Dash Srikanta
Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
Cancer Lett. 2003 Mar 20;192(1):49-57. doi: 10.1016/s0304-3835(02)00695-x.
Recent studies suggest that Epstein-Barr virus (EBV) may act as a helper virus for the development of hepatocellular carcinoma by promoting replication of the hepatitis C virus (HCV) in the infected liver. Detection of EBV DNA in a high percentage of HCV-positive human hepatocellular carcinomas (HCC) from Japanese patients has supported this concept. In order to determine whether EBV infection is associated with HCC, we examined paraffin-embedded tissues from 31 cases of non-cirrhotic livers with hepatocellular carcinoma for the presence of EBV, HCV and hepatitis B virus (HBV) infection. RNA prepared from tumor samples were used as a template for reverse transcription followed by double-nested PCR with primers for the 5' untranslated region (NT) of HCV. DNA extracts of tumor samples were tested by single polymerase chain reaction for the detection of EBV and HBV (X- and/or S-gene) DNA sequences. To control for nucleic acid integrity, all tumor samples were amplified for human beta-globin DNA by polymerase chain reaction and subjected to Southern blot hybridization. None of the cases was found to be positive for EBV. Ten HCC cases (32%) tested positive for HCV and 12 HCC cases (38%) tested positive for HBV. Six of the surveyed patients had nucleic acids of both HCV and HBV in their tumor tissue. All HCC tumor samples were positive for beta-globin. Our study shows that HCV and HBV infections, but not EBV infection, are associated with hepatocarcinogenesis in non-cirrhotic livers. Other unknown risk factors seem to be in effect in the development of hepatocellular carcinoma in non-cirrhotic livers.
最近的研究表明,爱泼斯坦-巴尔病毒(EBV)可能通过促进丙型肝炎病毒(HCV)在受感染肝脏中的复制,而成为肝细胞癌发生发展的辅助病毒。在日本患者的高比例HCV阳性人类肝细胞癌(HCC)中检测到EBV DNA,支持了这一概念。为了确定EBV感染是否与HCC相关,我们检查了31例非肝硬化肝细胞癌石蜡包埋组织中EBV、HCV和乙型肝炎病毒(HBV)感染情况。从肿瘤样本中提取的RNA用作逆转录模板,随后用针对HCV 5'非翻译区(NT)的引物进行双巢式PCR。肿瘤样本的DNA提取物通过单聚合酶链反应检测EBV和HBV(X和/或S基因)DNA序列。为了控制核酸完整性,所有肿瘤样本均通过聚合酶链反应扩增人β-珠蛋白DNA,并进行Southern印迹杂交。未发现任何病例EBV呈阳性。10例HCC病例(32%)HCV检测呈阳性,12例HCC病例(38%)HBV检测呈阳性。6名被调查患者的肿瘤组织中同时存在HCV和HBV核酸。所有HCC肿瘤样本β-珠蛋白均呈阳性。我们的研究表明,HCV和HBV感染而非EBV感染与非肝硬化肝脏中的肝癌发生相关。其他未知风险因素似乎在非肝硬化肝脏肝细胞癌的发生中起作用。