Liver Cancer
Copyright ©The Author(s) 2004. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 15, 2004; 10(8): 1141-1145
Published online Apr 15, 2004. doi: 10.3748/wjg.v10.i8.1141
Significant correlation between expression level of HSP gp96 and progression of hepatitis B virus induced diseases
Xiao-Dong Zhu, Cheng-Lin Li, Zhen-Wei Lang, George F Gao, Po Tien
Xiao-Dong Zhu, Po Tien, Department of Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080, China
Cheng-Lin Li, Zhen-Wei Lang, Department of Pathology, Beijing You’an Hospital, Beijing 100054, China
George F Gao, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford OX3 9DU, United Kingdom
Author contributions: All authors contributed equally to the work.
Supported by the Major State Basic Research Development Program of China (Program 973) (Grant No. 2001CB510001)
Correspondence to: Professor Po Tien, Department of Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Zhongguancun Beiyitiao, Beijing 100080, China. tienpo@sun.im.ac.cn
Telephone: +86-10-62554247 Fax: +86-10-62622101
Received: August 23, 2003
Revised: October 1, 2003
Accepted: October 12, 2003
Published online: April 15, 2004
Abstract

AIM: 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.

CONCLUSION: Increased expression of gp96 might be used as a diagnostic or prognostic bio-marker for the HBV infection and HBV-induced diseases.

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