Glypican-3 is a biomarker and a therapeutic target of hepatocellular carcinoma.

Abstract

BACKGROUND:

The carcinogenesis of hepatocellular carcinoma (HCC) is a multi-factorial, multi-step and complex process. Early diagnosis and effective treatments are of utmost importance. This review summarized the recent studies of oncofetal glypican-3 (GPC-3), a membrane-associated heparan sulfate proteoglycan, in the diagnosis and treatment of HCC.

DATA SOURCES:

English-language reports published from June 2001 to September 2014 were searched from MEDLINE. The key words searched included: GPC-3, biomarker, target and HCC. The sensitivity, specificity, positive and negative predictive values were extracted, and the effect of GPC-3 targeted therapy on HCC was also evaluated.

RESULTS:

GPC-3 plays a crucial role in HCC cell proliferation and metastasis. It mediates oncogenesis involving signaling pathways during hepatocyte malignant transformation. GPC-3 expression is increased in atypical hyperplasia and cancerous tissues. GPC-3 levels in HCC patients are related to HBV infection, TNM stage, periportal cancerous embolus, and extrahepatic metastasis. The diagnostic accuracy of the combination of serum GPC-3 and alpha-fetoprotein in HCC is up to 94.3%. Down-regulation of GPC-3 with specific siRNA or anti-GPC-3 antibody alters cell migration, metastasis and invasion behaviors. The nude mice xenograft tumor growth is inhibited by silencing GPC-3 gene transcription.

CONCLUSION:

Oncofetal GPC-3 is a highly specific biomarker for the diagnosis of HCC and a promising target molecule for HCC gene therapy.

• Authors: Li Wang, Min Yao, Liu-Hong Pan, Qi Qian, Deng-Fu Yao
• Journal: Hepatobiliary & pancreatic diseases international : HBPD INT (Hepatobiliary Pancreat Dis Int) Vol. 14 Issue 4 Pg. 361-6 (Aug 2015) ISSN: 1499-3872 [Print] Singapore
• PMID: 26256079 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Biomarkers, Tumor
• GPC3 protein, human
• Glypicans

Topics

• Animals
• Biomarkers, Tumor (genetics, metabolism)
• Carcinoma, Hepatocellular (genetics, metabolism, secondary, therapy)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Gene Expression Regulation, Neoplastic
• Genetic Therapy (methods)
• Glypicans (genetics, metabolism)
• Humans
• Liver Neoplasms (genetics, metabolism, pathology, therapy)
• Neoplasm Invasiveness
• Predictive Value of Tests
• Prognosis
• Signal Transduction (drug effects)