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...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.展开更多
AIM: To study Hepatitis B virus (HBV) infection and its association with hepatocellular carcinoma (HCC) at the miRNA level.METHODS: Three cellular models were used to investigate miRNA expression changes during HBV in...AIM: To study Hepatitis B virus (HBV) infection and its association with hepatocellular carcinoma (HCC) at the miRNA level.METHODS: Three cellular models were used to investigate miRNA expression changes during HBV infection: human HepG2 hepatoblastoma cell line as a model without HBV infection;HepG2 cell line transfected with a 1.3-fold full-length HBV genome as an acute infection model;and HepG2.2.15 cell line,which is derived from HepG2 and stably transfected with a complete HBV genome,as a chronic infection model.The miRNA levels were examined using microarray technology.To explore the relationship between HBV infection and HCC genesis at the miRNA level,we downloaded from national center for biotechnology information Gene Expression Omnibus an miRNA expression dataset derived from HCC patients,most of whom are HBV carriers.We compared the miRNA expression alterations during HBV infection with those in HCC patients,by analyzing miRNA expression change profiles statistically.RESULTS: Seventy-seven and 48 miRNAs were differentially expressed during acute and chronic HBV infection,respectively.Among these miRNAs,25 were in common,the intersection of which was significant under the hypergeometric test (P = 1.3 × 10-11).Fourteen miRNAs were observed to change coherently in the acute and chronic infections,with one upregulated and 13 downregulated.Eleven showed inverse changes during the two phases of infection;downregulated in the acute infection and upregulated in the chronic infection.The results imply that common and specific mechanisms exist at the miRNA level during acute and chronic HBV infection.Besides,comparative analysis of the miRNA expression changes during HBV infection with those in HCC indicates that,although miRNA expression changes during HBV infection are distinct from those in HCC patients (P < 2.2 × 10-16),they exhibited significant correlations (P = 0.0229 for acute infection;P = 0.0084 for chronic infection).Perturbation of miRNA expression during chronic HBV infection was closer to that in展开更多
基金Supported by the Major State Basic Research Development Program of China (Program 973) (Grant No.2001CB510001)
文摘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.
基金Supported by Ministry of Science and Technology of China,No.2007CB516810National Natural Science Foundation of China,Nos.30800971 and 30900270China Postdoctoral Science Foundation,No.20070420731
文摘AIM: To study Hepatitis B virus (HBV) infection and its association with hepatocellular carcinoma (HCC) at the miRNA level.METHODS: Three cellular models were used to investigate miRNA expression changes during HBV infection: human HepG2 hepatoblastoma cell line as a model without HBV infection;HepG2 cell line transfected with a 1.3-fold full-length HBV genome as an acute infection model;and HepG2.2.15 cell line,which is derived from HepG2 and stably transfected with a complete HBV genome,as a chronic infection model.The miRNA levels were examined using microarray technology.To explore the relationship between HBV infection and HCC genesis at the miRNA level,we downloaded from national center for biotechnology information Gene Expression Omnibus an miRNA expression dataset derived from HCC patients,most of whom are HBV carriers.We compared the miRNA expression alterations during HBV infection with those in HCC patients,by analyzing miRNA expression change profiles statistically.RESULTS: Seventy-seven and 48 miRNAs were differentially expressed during acute and chronic HBV infection,respectively.Among these miRNAs,25 were in common,the intersection of which was significant under the hypergeometric test (P = 1.3 × 10-11).Fourteen miRNAs were observed to change coherently in the acute and chronic infections,with one upregulated and 13 downregulated.Eleven showed inverse changes during the two phases of infection;downregulated in the acute infection and upregulated in the chronic infection.The results imply that common and specific mechanisms exist at the miRNA level during acute and chronic HBV infection.Besides,comparative analysis of the miRNA expression changes during HBV infection with those in HCC indicates that,although miRNA expression changes during HBV infection are distinct from those in HCC patients (P < 2.2 × 10-16),they exhibited significant correlations (P = 0.0229 for acute infection;P = 0.0084 for chronic infection).Perturbation of miRNA expression during chronic HBV infection was closer to that in
