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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 7, 2015; 21(37): 10584-10597
Published online Oct 7, 2015. doi: 10.3748/wjg.v21.i37.10584
Genetic and epigenetic aspects of initiation and progression of hepatocellular carcinoma
Mitsuro Kanda, Hiroyuki Sugimoto, Yasuhiro Kodera
Mitsuro Kanda, Hiroyuki Sugimoto, Yasuhiro Kodera, Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
Author contributions: Kanda M wrote the manuscript; Sugimoto H and Kodera Y revised the manuscript for important intellectual content.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Mitsuro Kanda, MD, PhD, Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. m-kanda@med.nagoya-u.ac.jp
Telephone: +81-52-7442249 Fax: +81-52-7442255
Received: March 24, 2015
Peer-review started: March 27, 2015
First decision: April 24, 2015
Revised: May 8, 2015
Accepted: September 2, 2015
Article in press: September 2, 2015
Published online: October 7, 2015
Processing time: 188 Days and 2.6 Hours
Abstract

Hepatocellular carcinoma (HCC) is a primary cancer of the liver that is predominant in developing countries and is responsible for nearly 600000 deaths each year worldwide. Similar to many other tumors, the development of HCC must be understood as a multistep process involving the accumulation of genetic and epigenetic alterations in regulatory genes, leading to the activation of oncogenes and the inactivation or loss of tumor suppressor genes. Extensive research over the past decade has identified a number of molecular biomarkers, including aberrant expression of HCC-related genes and microRNAs. The challenge facing HCC research and clinical care at this time is to address the heterogeneity and complexity of these genetic and epigenetic alterations and to use this information to direct rational diagnosis and treatment strategies. The multikinase inhibitor sorafenib was the first molecularly targeted drug for HCC to show some extent of survival benefits in patients with advanced tumors. Although the results obtained using sorafenib support the importance of molecular therapies in the treatment of HCC, there is still room for improvement. In addition, no molecular markers for drug sensitivity, recurrence and prognosis are currently clinically available. In this review, we provide an overview of recently published articles addressing HCC-related genes and microRNAs to update what is currently known regarding genetic and epigenetic aspects of the pathogenesis of HCC and propose novel promising candidates for use as diagnostic and therapeutic targets in HCC.

Keywords: Hepatocellular carcinoma; Oncogene; Tumor suppressor gene; MicroRNA; DNA methylation

Core tip: Despite the large number of studies dedicated to the molecular diagnosis of hepatocellular carcinoma (HCC), highly sensitive biomarkers of the initiation and progression of HCC still need to be identified. At the same time, the development of novel molecular targeting agents that can surpass the effect of the multikinase inhibitor sorafenib is much-anticipated. This review aimed to update our knowledge of genetic and epigenetic aspects of HCC by providing an overview of novel HCC-related genes and microRNAs as candidates for use as diagnostic and therapeutic targets in HCC.