Significant correlation between expression level of HSP gp96 and progression of hepatitis B virus induced diseases.
OBJECTIVE
Gp96, also known as Grp94, is a member of heat shock protein (HSP) family and binds repertoires of peptides thereof eliciting peptide-specific T cell immune responses. It predominantly locates inside the endoplasmic reticulum (ER) with some cell surface expression in certain cancerous cells. Previous studies have shown that gp96 expression level was up-regulated in tumor cells, including hepatocellular carcinoma (HCC). However, relationship between the extent of gp96 expression and disease progression especially HBV-induced chronic infection, cirrhosis and hepatocellular carcinoma, has not been addressed before. As primary HCC can be induced and progressed from chronic hepatitis B virus (HBV) infection and HBV-induced cirrhosis, we designed an immunohistochemical experiment to test the correlation between gp96 expression level and HBV-induced disease progression, from chronic HBV infection, cirrhosis to HCC.


METHODS
We chose liver samples from different patients of hepatitis B virus induced diseases, including chronic hepatitis B (77 patients), cirrhosis (27 patients) and primary HCC (30 patients), to test the expression level of gp96 in different affected groups. Formalin-fixed, and paraffin-embedded liver tissues taken from these patients were immuno-stained by using an anti-gp96 monoclonal antibody for the expression level of gp96 protein in the sections. In addition, Western blotting of whole cell lysates derived from established human embryonic liver cell lines and several human HCC cell lines (Huh7, HepG2, SSMC-7721) was compared with the expression of gp96.


RESULTS
We found that the extent of elevated gp96 expression was significantly correlated with the disease progression, and was the highest in HCC patients, lowest in chronic HBV infection and was that of the cirrhosis in the middle.


CONCLUSIONS
Increased expression of gp96 might be used as a diagnostic or prognostic bio-marker for the HBV infection and HBV-induced diseases.
Zhu
Xiao-Dong
XD
Department of Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Zhongguancun Beiyitiao, Beijing 100080, China.
Li
Cheng-Lin
CL
Lang
Zhen-Wei
ZW
Gao
George F
GF
Tien
Po
P
D000951:Antigens, Neoplasm / Q000378:metabolism*; D015415:Biomarkers; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D045744:Cell Line, Tumor; D018450:Disease Progression; D019694:Hepatitis B, Chronic / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology
D000951:Antigens, Neoplasm; D015415:Biomarkers; C052646:sarcoma glycoprotein gp96 rejection antigens