Abstract 4425: Specific miRNA expression profiles of non-tumor liver tissues predict the risk for multicentric occurrence of hepatocellular carcinoma
Authors: Utsunomiya Tohru , Shimada Mitsuo , Imura Satoru , Morine Yuji , Ikemoto Tetsuya , Morine Hiroki , Hanaoka Jun , Sugimoto Koji , Saito Yuji , Asanoma Michihito , Yamada Shinichiro 
Published: August 2012

Abstract
Background: It is reasonable to investigate the non-tumor liver tissues to predict a risk for development of hepatocellular carcinoma (HCC). We have previously reported that specific gene-expression profiles of non-tumor liver tissues (up-regulation of STMN1, down-regulation of CYP1A2, etc.) can predict the risk for multicentric (MC) occurrence of HCC. In this study, we thus examined whether specific miRNA expression patterns of non-tumor liver tissues could also predict the risk for MC occurrence of HCC. In addition, characteristics of miRNAs associated with the development of HCC were investigated. Methods: 1. We divided the 35 HCC patients, who underwent hepatectomy, into 3 groups based on the etiological factors of HCC; hepatitis B virus (HBV, n=10), hepatitis C virus (HCV, n=7), and non-B non-C (NBNC, n=18). Non-tumor liver tissues from 3 patients with metastatic liver tumors served as normal control (NC). We analyzed miRNA expressions in non-tumor liver tissues using a miRNA microarray (Agilent Technologies, 866 probes), and compared between each HCC group and the NC group. 2. We divided the 20 HCC patients, who underwent hepatectomy, into 2 groups; non-MC group (no MC recurrence more than 3 years, n=10) and MC group (MC recurrence within 3 years after hepatectomy, n=10). We identified specific miRNA expression patterns associated with MC recurrence. Results: 1. A hierarchical clustering analysis clearly divided each HCC group and the NC group. Compared to the NC group, 25 miRNA, such as let-7 family, miR-451/144 family, miR-10b, miR-16, miR-26b, miR-223, miR-326, and miR-328 were significantly down-regulated in the NBNC group. Interestingly, most of these miRNAs were associated with the expressions of caner stem cell markers, such as CD44, CD133, AVCC1, ABCG2, and MDR1. In addition, miR-494, which reduces the PTEN expression, was up-regulated in both the HCV and NBNC group compared to the NC group. The expression of miR-328, which reduces the ABCG2 (BCRP1) expression, was validated using RT-PCR. 2. A hierarchical clustering analysis divided the non-MC group and the MC group. The MC recurrence-related miRNA included let-7, miR-328, and miR18a*, which regulates K-ras gene expression. Conclusions: The risk for MC recurrence of HCC may possibly be predicted by not only the specific gene-expression profiles but also the specific miRNA expression profiles of non-tumor liver tissues in HCC patients. Moreover, the down-regulation of specific miRNAs, which inhibit the expressions of caner stem cell markers, may be associated with the MC occurrence of HCC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4425. doi:1538-7445.AM2012-4425