Affiliations: [a] Department of Hemato-Oncology, Yuseong Sun Hospital, Daejeon, Korea | [b] Department of Pharmacology, College of Pharmacy, Kyung Hee University, Seoul, Korea | [c] Department of Life and Nanopharmaceutical Science, Graduate School, Kyung Hee University, Seoul, Korea
Correspondence:
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Corresponding author: Jin Woo Choi, Department of Pharmacology, College of Pharmacy, Kyung Hee University, 7-13, Kyungheedae-ro 6-gil, Dongdaemun-gu, Seoul 02453, Korea. Tel.: +82 10 4047 3070; Fax: +82 2 961 9580; E-mail: [email protected].
Abstract: BACKGROUND: Hepatitis B virus (HBV) accounts for more than 60% of hepatocellular carcinoma (HCC) cases. However, there is limited information about the features of HBV-driven HCC that differentiate it from other types of HCC. OBJECTIVE: The aim of this study is to find a gene specific to HBV-driven HCC and understand its role during tumorigenesis. METHODS: The differences in gene expression patterns were analyzed among patients with hepatitis virus-unrelated liver cirrhosis, and hepatitis C virus- and HBV-driven HCC. Genes expressed only in HBV patients were compared to genes of transgenic mice expressing hepatitis B viral X gene. RESULTS: Integrin α6 was commonly overexpressed in both HBV-driven HCC patients and transgenic mice expressing viral X. This gene’s activation induced overexpression of integrin α6, as well as formation of integrins α6β1 and α6β4, without changing the expression of non-integrin laminin receptors. Suppression of integrin α6 caused significant inhibition of tumor migration in vitro. CONCLUSIONS: This study found a significant association between HBV and integrin α6, which may be responsible for early migration and invasion of HCC. Thus, integrin α6 is a predictive marker for tumor recurrence and invasiveness of HBV-driven HCC.
Keywords: Hepatocellular carcinoma, integrin, hepatitis B virus, hepatitis B viral X gene
