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


CONCLUSIONS
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.
Wang
Xiao-Zhong
XZ
Department of Gastroenterology, Affiliated Union Hospital, Fujian Medical University, Fuzhou 350001, Fujian Province, China. drwangxz@pub6.fz.fj.cn
Chen
Xiao-Chun
XC
Chen
Yun-Xin
YX
Zhang
Li-Juan
LJ
Li
Dan
D
Chen
Feng-Lin
FL
Chen
Zhi-Xin
ZX
Chen
Hong-Ying
HY
Tao
Qi-Ming
QM
D006528:Carcinoma, Hepatocellular / Q000601:surgery / Q000821:virology*; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D006511:Hepatitis B Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000302:isolation & purification; D006801:Humans; D008113:Liver Neoplasms / Q000601:surgery / Q000821:virology*; D008562:Membrane Glycoproteins / Q000032:analysis / Q000097:blood*; D012016:Reference Values; D015534:Trans-Activators / Q000032:analysis / Q000097:blood / Q000235:genetics*; D054334:Viral Regulatory and Accessory Proteins; D019014:fas Receptor / Q000032:analysis / Q000097:blood*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D006511:Hepatitis B Antigens; D008562:Membrane Glycoproteins; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; D019014:fas Receptor; C057628:hepatitis B virus X protein