Values of circulating GPC-3 mRNA and alpha-fetoprotein in detecting patients with hepatocellular carcinoma

Hepatobiliary Pancreat Dis Int. 2013 Apr;12(2):171-9. doi: 10.1016/s1499-3872(13)60028-4.


Background: The prognosis of hepatocellular carcinoma (HCC) is poor and its early diagnosis is of the utmost importance. This study aimed to investigate the values of glypican-3 (GPC-3) expression in the liver and sera and its gene transcription for diagnosis and monitoring of metastasis of HCC.

Methods: Liver GPC-3 was analyzed in HCC tissues from 36 patients by immunohistochemistry and Western blotting. GPC-3 mRNA from circulating peripheral blood mononuclear cells from 123 HCC patients or 246 patients with other diseases or 36 HCC tissues was amplified by RT-PCR, quantitative real-time PCR, and confirmed by DNA sequencing. Circulating GPC-3 level was detected by ELISA.

Results: The increasing expression of GPC-3 was observed from non-cancerous to cancerous tissues, with brown granule-like staining localized in tumor parts of atypical hyperplasia and HCC formation. The positive rate of GPC-3 was 80.6% in HCC, 41.7% in their paracancerous tissues, and none in distal cancerous tissues (P<0.001), with no significant difference in differentiation grade and tumor number except for size (Z=2.941, P=0.003). Serum GPC-3 was detected only in HCC (52.8%) and significant difference was found between GPC-3 and tumor size (X2=6.318, P=0.012) or HBV infection (X2=23.362, P<0.001). Circulating GPC-3 mRNA was detected in 70.7% of HCC tissues, with relation to TNM stage, periportal cancerous embolus, and extra-hepatic metastasis (P<0.001). The combination of circulating GPC-3, GPC-3 mRNA and alpha-fetoprotein is of complementary value for HCC diagnosis (94.3%).

Conclusion: Both GPC-3 overexpression and GPC-3 mRNA abnormality could be used as markers for the diagnosis of HCC and monitoring its metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Blotting, Western
  • Carcinoma, Hepatocellular / blood*
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / secondary
  • Case-Control Studies
  • Chi-Square Distribution
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glypicans / genetics*
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / blood*
  • Liver Neoplasms / chemistry
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • RNA, Messenger / blood*
  • Real-Time Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Up-Regulation
  • alpha-Fetoproteins / analysis*


  • AFP protein, human
  • GPC3 protein, human
  • Glypicans
  • RNA, Messenger
  • alpha-Fetoproteins