Proteomic analysis of HCV cirrhosis and HCV-induced HCC: identifying biomarkers for monitoring HCV-cirrhotic patients awaiting liver transplantation.
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.
Mas
Valeria R
VR
Division of Transplantation, Department of Surgery, Virginia Commonwealth University, Richmond, VA, USA. vrmas@hsc.vcu.edu
Maluf
Daniel G
DG
Archer
Kellie J
KJ
Yanek
Kenneth
K
Bornstein
Karen
K
Fisher
Robert A
RA
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
D015415:Biomarkers; D014168:Transferrin