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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2016; 22(1): 275-283
Published online Jan 7, 2016. doi: 10.3748/wjg.v22.i1.275
Glypican-3 is a prognostic factor and an immunotherapeutic target in hepatocellular carcinoma
Yukihiro Haruyama, Hiroaki Kataoka
Yukihiro Haruyama, Hiroaki Kataoka, Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan
Author contributions: Haruyama Y and Kataoka H contributed equally to this work; Haruyama Y and Kataoka H designed the review style, reviewed literatures and wrote the paper.
Supported by Collaborative Research Fund from Chugai Pharmaceutical Co. (to Kataoka H); and Grant-in-Aid from The Ministry of Education, Culuture, Sports, Science and Technology, Japan, No. 24390099 (to Kataoka H).
Conflict-of-interest statement: Kataoka H receives collaborative research funding from Chugai Pharmaceutical Co. Haruyama Y declares no potential conflicts of interest with respect to this article.
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: Hiroaki Kataoka, MD, PhD, Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan. mejina@med.miyazaki-u.ac.jp
Telephone: +81-985-852809 Fax: +81-985-856003
Received: May 25, 2015
Peer-review started: May 27, 2015
First decision: August 31, 2015
Revised: October 29, 2015
Accepted: November 19, 2015
Article in press: November 19, 2015
Published online: January 7, 2016
Processing time: 220 Days and 4 Hours
Abstract

Glypican-3 (GPC3) is a cell surface oncofetal proteoglycan that is anchored by glycosylphosphatidylinositol. Whereas GPC3 is abundant in fetal liver, its expression is hardly detectable in adult liver. Importantly, GPC3 is overexpressed in hepatocellular carcinoma (HCC), and several immunohistochemical studies reported that overexpression predicts a poorer prognosis for HCC patients. Therefore, GPC3 would serve as a useful molecular marker for HCC diagnosis and also as a target for therapeutic intervention in HCC. Indeed, some immunotherapy protocols targeting GPC3 are under investigations; those include humanized anti-GPC3 cytotoxic antibody, peptide vaccine and immunotoxin therapies. When considering the clinical requirements for GPC3-targeting therapy, companion diagnostics to select the appropriate HCC patients are critical, and both immunohistochemical analysis of tissue sections and measurement of serum GPC3 level have been suggested for this purpose. This review summarizes current knowledge regarding the clinical implication of GPC3 detection and targeting in the management of patients with HCC.

Keywords: Glypican-3; Enzyme-linked immunosorbent assay; Hepatocellular carcinoma; Prognosis; Companion diagnostics; Immunohistochemistry

Core tip: Glypican-3 is frequently overexpressed in hepatocellular carcinoma (HCC). Accumulating evidence indicates that high glypican-3 expression is a significant prognostic factor that predicts poor outcome of patients with HCC. Thus, it serves as a promising molecular target for the development of novel therapies for HCC, and preclinical and clinical trials targeting glypican-3 are currently underway. Evaluation of the glypican-3 levels in HCC tissues or in sera of patients with HCC would be of value for predicting the patients’ prognosis and companion diagnostics for future glypican-3-targeting therapies.