Host: Japan Society for Clinical Proteomics
We performed proteomic profiling of cancerous and paired non-cancerous tissues from Japanese HCC patients with HCV infection but not with hepatitis B virus infection or chronic alcoholic hepatitis by two-dimensional gel electrophoresis(2DE), tandem mass spectrometry(MS/MS), immunoblotting and immunohistochemical analysis. In the cancerous tissues HSP70 family proteins such as GRP78, HSC70, GRP75 and HSP70.1, HSP60, glutamine synthetase (GS), alpha-enolase (ENOA), phosphoglycerate mutase-1, triose phosphate isomerase and ATP synthase beta chain were increased two-fold more than in non-cancerous tissues. On the contrary almumin, ferritin light chain, smoothelin, tropomyosin beta chain, arginase 1, aldolase B, ketohexokinase and enoyl-CoA hydratase were decreased less than a half. Further examinations indicated that GS isoforms were much increased in highly differentiated HCC, and ENOA increased in poorly differentiated HCC which correlated positively with tumor size and venous invasion. We also performed PROTEOMEX in which antigenic proteins in cancerous tissues could be detected by 2DE-immunoblot and MS/MS analysis with autoantibodies in sera from HCC patients nad from healthy control. The candidates for the antigenic proteins were determined to be HSP70, peroxiredoxin and MnSOD. From these results we will discuss on possible molecular mechanisms for hepatocarcinogenesis by HCV infection and potential use of those proteins for clinical diagnosis of HCC in early stage and for immunotherapy of HCC.
