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Glypican-3 is a biomarker and a therapeutic target of hepatocellular carcinoma |
Li Wang, Min Yao, Liu-Hong Pan, Qi Qian and Deng-Fu Yao |
Nantong, China
Author Affiliations: Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China (Wang L, Pan LH, Qian Q and Yao DF); Departments of Medical Informatics (Wang L) and Immunology (Yao M), Medical School of Nantong University, Nantong 226001, China
Corresponding Author: Deng-Fu Yao, MD, PhD, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, 20 West Temple Road, Nantong 226001, China (Tel: +86-513-85052297; Fax: +86- 513-85052254; Email: yaodf@ahnmc.com) |
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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.
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