Overexpression of HBxAg in hepatocellular carcinoma and its relationship with Fas/FasL system

World J Gastroenterol. 2003 Dec;9(12):2671-5. doi: 10.3748/wjg.v9.i12.2671.

Abstract

Aim: To study the expression and serum level of HBxAg, Fas and FasL in tissues of HCC patients, and to assess the relationship between HBxAg and Fas/FasL system.

Methods: Tissues from 50 patients with HCC were tested for the expression of HBxAg, Fas and FasL by S-P immunohistochemistry. Serum levels of sFas/sFasL and HBsAg/HBeAg were measured by ELISA assay. HBV X gene was detected by PCR in serum and confirmed by automatic sequencing. Fifty cases of liver cirrhosis and 30 normal controls were involved in serum analysis.

Results: The expression of HBxAg, Fas and FasL in carcinoma tissues was 96 %, 84 % and 98 %, respectively. Staining of HBxAg, Fas and FasL was observed predominately in cytoplasms, no significant difference was found in intensity between HBxAg, Fas and FasL (P>0.05). HBxAg, Fas and FasL might express in the same area of carcinoma tissues and this co-expression could be found in most patients with HCC. The mean levels of sFas in serum from HCC, cirrhosis and normal controls were 762.29 +/- 391.56 microg.L(-1), 835.36 +/- 407.33 microg.L(-1) and 238.27 +/- 135.29 microg.L(-1). The mean levels of sFasL in serum from HCC, cirrhosis and normal controls were 156.36 +/- 9.61 microg.L(-1), 173.63 +/- 18.74 microg.L(-1) and 121.96 +/- 7.83 microg.L(-1). Statistical analysis showed that both sFas and sFasL in HCC and cirrhosis patients were significantly higher than those in normal controls (P<0.01). Serum HBV X gene was found in 32% of HCC patients and 46% of cirrhotic patients. There was no significant relationship between serum level of sFas/sFasL and serum X gene detection (P>0.05). Eight percent of HCC patients with negative HBsAg and HBeAg in serum might have X gene in serum and HBxAg expression in carcinoma tissues.

Conclusion: Our data suggest that HBxAg and Fas/FasL system plays an important role in the development of human HCC. Expression of HBxAg can leads to expression of Fas/FasL system which and reverse apoptosis of hepatocellular carcinoma induced by FasL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / surgery
  • Carcinoma, Hepatocellular / virology*
  • Enzyme-Linked Immunosorbent Assay
  • Fas Ligand Protein
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Regulation, Viral
  • Hepatitis B Antigens / genetics*
  • Hepatitis B virus / isolation & purification
  • Humans
  • Liver Neoplasms / surgery
  • Liver Neoplasms / virology*
  • Membrane Glycoproteins / analysis
  • Membrane Glycoproteins / blood*
  • Reference Values
  • Trans-Activators / analysis
  • Trans-Activators / blood
  • Trans-Activators / genetics*
  • Viral Regulatory and Accessory Proteins
  • fas Receptor / analysis
  • fas Receptor / blood*

Substances

  • FASLG protein, human
  • Fas Ligand Protein
  • Hepatitis B Antigens
  • Membrane Glycoproteins
  • Trans-Activators
  • Viral Regulatory and Accessory Proteins
  • fas Receptor
  • hepatitis B virus X protein