title: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  Oncofetal GPC-3 is a highly specific biomarker for the diagnosis of HCC and a promising target molecule for HCC gene therapy.
authors.affiliation: Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China. yaodf@ahnmc.com.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Yao
authors.forename: Liu-Hong
authors.initials: LH
authors.lastname: Pan
authors.forename: Qi
authors.initials: Q
authors.lastname: Qian
authors.forename: Deng-Fu
authors.initials: DF
authors.lastname: Yao
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000556:secondary / Q000628:therapy*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods*; D053673:Glypicans / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D009361:Neoplasm Invasiveness; D011237:Predictive Value of Tests; D011379:Prognosis; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D014408:Biomarkers, Tumor; C105937:GPC3 protein, human; D053673:Glypicans