Published online Jan 7, 2016. doi: 10.3748/wjg.v22.i1.275
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
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.
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.