摘要
BACKGROUND： The carcinogenesis of hepatocellular car- cinoma （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 on- cofetal glypican-3 （GPC-3）, a membrane-associated heparan sulfate proteoglycan, in the diagnosis and treatment of HCC. DATA SOURCES： English-language reports published from Iune 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 tar- geted therapy on HCC was also evaluated. RESULTS： GPC-3 plays a crucial role in HCC cell prolifera- tion and metastasis. It mediates oncogenesis involving signal- ing 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 biomark- er for the diagnosis of HCC and a promising target molecule for HCC gene therapy.
BACKGROUND： The carcinogenesis of hepatocellular car- cinoma （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 on- cofetal glypican-3 （GPC-3）, a membrane-associated heparan sulfate proteoglycan, in the diagnosis and treatment of HCC. DATA SOURCES： English-language reports published from Iune 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 tar- geted therapy on HCC was also evaluated. RESULTS： GPC-3 plays a crucial role in HCC cell prolifera- tion and metastasis. It mediates oncogenesis involving signal- ing 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 biomark- er for the diagnosis of HCC and a promising target molecule for HCC gene therapy.
基金
supported in part by the grants from the Projects of Jiangsu Medical Science(2013-WSW-011,2014-YY-028 and HK201102)
the Qinglan and PAPD of Jiangsu Higher Education
the Nantong Undertaking and Technological Innovation(H2014078)
the International S&T Cooperation Program(2013DFA32150)of China
