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World J Gastroenterol. Oct 21, 2008; 14(39): 6072-6077
Published online Oct 21, 2008. doi: 10.3748/wjg.14.6072
Distinct expression patterns in hepatitis B virus- and hepatitis C virus-infected hepatocellular carcinoma
Chun-Feng Lee, Zhi-Qiang Ling, Ting Zhao, Kuan-Rong Lee
Chun-Feng Lee, Kuan-Rong Lee, Institute of Molecular Medicine, National Tsing Hua University, 101, Section 2, Kuang-Fu Road, Hsinchu, Taiwan 30013, China
Zhi-Qiang Ling, Zhejiang Cancer Research Institute, 38 Guangji Road Banshanqiao, Hangzhou 310022, Zhejiang Province, China
Ting Zhao, Department of surgery, Zhejiang Provincial People Hospital, 158 Shangtang Road, Hangzhou 310014, Zhejiang Province, China
Author contributions: Lee CF performed most of the experiments, participated in most of the data analysis and drafted the manuscript; Lee KR was the leader of the project, who conceived the study, designed the research, guided the experiments and the data analyses, and suggested revisions in the manuscript; Ling ZQ carried out cDNA microarray, real-time RT-PCR experiments and provided critical comments and suggested revisions in the manuscript; Zhao T collected and prepared hepatocellular carcinoma samples, and participated in some experiments; All authors read and approved the final manuscript.
Correspondence to: Kuan-Rong Lee, Institute of Molecular Medicine, National Tsing Hua University, 101, Section 2, Kuang-Fu Road, Hsinchu, Taiwan 30013, China. krlee@mx.nthu.edu.tw
Telephone: +886-3-574-2755 Fax: +886-3-571-5934
Received: September 1, 2008
Revised: September 8, 2008
Accepted: September 15, 2008
Published online: October 21, 2008
Abstract

AIM: To identify biomarkers indicating virus-specific hepatocarcinogenic process, differential mRNA expression in 32 patients with hepatitis B virus (HBV)-/hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) were investigated by means of cDNA microarrays comprising of 886 genes.

METHODS: Thirty two HCC patients were divided into two groups based on viral markers: hepatitis B virus positive and HCV positive. The expression profiles of 32 pairs of specimens (tumorous and surrounding non-tumorous liver tissues), consisting of 886 genes were analyzed.

RESULTS: Seven up-regulated genes in HBV-associated HCC comprised genes involved in protein synthesis (RPS5), cytoskeletal organization (KRT8), apoptosis related genes (CFLAR), transport (ATP5F1), cell membrane receptor related genes (IGFBP2), signal transduction or transcription related genes (MAP3K5), and metastasis-related genes (MMP9). The up-regulated genes in HCV-infected group included 4 genes: VIM (cell structure), ACTB (cell structure), GAPD (glycolysis) and CD58 (cell adhesion). The expression patterns of the 11 genes, identified by cDNA microarray, were confirmed by quantitative RT-PCR in 32 specimens.

CONCLUSION: The patterns of all identified genes were classified based on the viral factor involved in HBV- and HCV-associated HCC. Our results strongly suggest that the pattern of gene expression in HCC is closely associated with the etiologic factor. The present study indicates that HBV and HCV cause hepatocarcinogenesis by different mechanisms, and provide novel tools for the diagnosis and treatment of HBV- and HCV-associated HCC.

Keywords: Hepatocellular carcinoma, Hepatitis B virus, Hepatitis C virus-infected, cDNA microarray, Expression profiling