Identification of candidate biomarkers for hepatocellular carcinoma in plasma of HCV-infected cirrhotic patients by 2-D DIGE.
BACKGROUND
The current methods available for screening and detecting hepatocellular carcinoma (HCC) have insufficient sensitivity and specificity, and only a low percentage of diagnosis of small tumours is based on these assays. Because HCC is usually asymptomatic at potentially curative stages, identification of biomarkers for the early detection of HCC is essential to improve patient survival.


OBJECTIVE
The aim of this study was to identify candidate markers for HCC development in the plasma from hepatitis C virus (HCV)-infected cirrhotic patients.


METHODS
We compared protein expression profiles of plasma samples from HCV-infected cirrhotic patients with and without HCC, using two-dimensional fluorescence difference gel electrophoresis (2-D DIGE) coupled with MALDI-TOF/TOF mass spectrometry. The 2-D DIGE results were analysed statistically using Decyder™ software, and verified by western blot and enzyme-linked immunosorbent assay (ELISA).


RESULTS
In the plasma of HCV-infected HCC patients, we observed decreased expression of complement component 9, ficolin-3 (FCN3), serum amyloid P component (SAP), fibrinogen-gamma and immunoglobulin gamma-1 chain, and increased expression of vitronectin (VTN) and galectin-3 binding protein (G3BP) by DIGE analysis. ELISA confirmed DIGE results for VTN and G3BP but not for SAP or FCN3 in a larger patient population.


CONCLUSIONS
The proteins VTN and SAP are candidate biomarkers for HCC development in HCV-infected cirrhotic patients.
Maimónides Institute for Biomedical Research in Córdoba (IMBIC), Reina Sofía University Hospital, University of Córdoba, Córdoba, Spain; Networked Biomedical Research Center, Hepatic and Digestive Diseases (CIBERehd), Barcelona, Spain.
Gustavo
G
Ferrín
Isidora
I
Ranchal
Camilo
C
Llamoza
Manuel L
ML
Rodríguez-Perálvarez
Antonio
A
Romero-Ruiz
Patricia
P
Aguilar-Melero
Pedro
P
López-Cillero
Javier
J
Briceño
Jordi
J
Muntané
José L
JL
Montero-Álvarez
Manuel
M
De la Mata
D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000175:diagnosis*; D042241:Early Diagnosis; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016174:Hepacivirus; D006526:Hepatitis C / Q000097:blood* / Q000150:complications; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000821:virology*; D008113:Liver Neoplasms / Q000097:blood / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D040901:Proteomics; D000683:Serum Amyloid P-Component / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D019096:Vitronectin / Q000097:blood
D014408:Biomarkers, Tumor; D000683:Serum Amyloid P-Component; D019096:Vitronectin
acute-phase proteins; cirrhosis; early diagnosis of cancer; liver cancer; tumour markers