title: Proteomic analysis of HCV cirrhosis and HCV-induced HCC: identifying biomarkers for monitoring HCV-cirrhotic patients awaiting liver transplantation.
abstract: BACKGROUND
  Progression from chronic hepatitis C virus (HCV) infection to cirrhosis and hepatocellular carcinoma (HCC) results in protein changes in the peripheral blood. We evaluated global protein expression in plasma samples of HCV-cirrhotic and HCV-cirrhotic-HCC patients.
  
  
  METHODS
  Plasma samples from 25 HCV-cirrhotic-HCC and 10 HCV-cirrhotic patients were quantitatively evaluated for protein expression. Tryptic peptides were analyzed using Thermo linear ion-trap mass spectrometer (LTQ) coupled with a Surveyor HPLC system (Thermo). SEQUEST and X!Tandem database search algorithms were used for peptide sequence identification. Protein relative quantification was performed using the area under the curve from the select ion chromatogram. A significant fold change between groups was based on controlling the false discovery rate (FDR) at less than 5%.
  
  
  RESULTS
  We identified and quantified 2320 proteins from the analysis of the different protein pattern between HCV-cirrhosis and HCV-HCC samples. Gene ontology terms classified the more important biologic process related to these proteins as signal transduction, regulation of transcription DNA-dependent, protein amino acid phosphorylation, cell adhesion, transport, and immune response. Seven proteins showed significant expression changes with a FDR less than 5% between cirrhosis and tumor groups. Moreover, 18 proteins showed significant expression changes (FDR <5%) when plasma samples from HCV-cirrhosis were compared with early HCV-HCC.
  
  
  CONCLUSIONS
  Differential protein expression was observed between samples from HCV patients with cirrhosis with and without HCC. Also, differences were observed between early and advanced HCV-HCC samples. This study provides important information for discovery of potential biomarkers for early HCC diagnosis in HCV cirrhotic patients.
authors.affiliation: Division of Transplantation, Department of Surgery, Virginia Commonwealth University, Richmond, VA, USA. vrmas@hsc.vcu.edu
authors.forename: Valeria R
authors.initials: VR
authors.lastname: Mas
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Maluf
authors.forename: Kellie J
authors.initials: KJ
authors.lastname: Archer
authors.forename: Kenneth
authors.initials: K
authors.lastname: Yanek
authors.forename: Karen
authors.initials: K
authors.lastname: Bornstein
authors.forename: Robert A
authors.initials: RA
authors.lastname: Fisher
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002645:Chickens; D006526:Hepatitis C / Q000150:complications / Q000378:metabolism*; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology / Q000378:metabolism*; D008113:Liver Neoplasms / Q000209:etiology / Q000378:metabolism*; D016031:Liver Transplantation; D009367:Neoplasm Staging; D040901:Proteomics; D014168:Transferrin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D014168:Transferrin