Brief Article
Copyright ©2010 Baishideng. All rights reserved.
World J Hepatol. Mar 27, 2010; 2(3): 127-135
Published online Mar 27, 2010. doi: 10.4254/wjh.v2.i3.127
Proteomic analysis for developing new biomarkers of hepatocellular carcinoma
Maria Pleguezuelo, Laura M Lopez-Sanchez, Antonio Rodriguez-Ariza, Jose L Montero, Javier Briceno, Ruben Ciria, Jordi Muntane, Manuel de la Mata
Maria Pleguezuelo, Ruben Ciria, Liver Research Unit and Academic Department of Surgery, Reina Sofia University Hospital, Avda Menendez Pidal s/n, Cordoba 14004, Spain
Laura M Lopez-Sanchez, Antonio Rodriguez-Ariza, Research Unit, Reina Sofia University Hospital, Avda Menendez Pidal s/n, Cordoba 14004, Spain
Jose L Montero, Javier Briceno, Jordi Muntane, Manuel de la Mata, Liver Research Unit and Academic Department of Surgery, CIBERehd, Reina Sofia University Hospital, Avda Menendez Pidal s/n, Cordoba 14004, Spain
Author contributions: Pleguezuelo M, Montero JL and de la Mata M designed the research; Pleguezuelo M, Lopez-Sanchez LM and Rodriguez-Ariza A performed the research; Pleguezuelo M, Ciria R and Briceno J performed the statistical analysis and wrote the paper; de la Mata M, Rodriguez-Ariza A and Muntane J revised the manuscript critically.
Supported by the Centrode Investigacion Biomedicaen Reden Enfermedades Hepaticasy Digestivas (CIBERehd)
Correspondence to: Maria Pleguezuelo, MD, PhD, Liver Research Unit and Academic Department of Surgery, Reina Sofia University Hospital, Avda Menendez Pidal s/n, Cordoba 14004, Spain. plegue3@hotmail.com
Telephone: +34-957-010328 Fax: +34-957-736014
Received: October 21, 2009
Revised: January 14, 2010
Accepted: January 21, 2010
Published online: March 27, 2010
Abstract

AIM: To identify new markers of hepatocellular carcinoma (HCC) using a proteomic analysis.

METHODS: Patients with liver cirrhosis of the three most frequent etiologies: hepatitis C virus, hepatitis B virus and alcoholic liver disease, were included in the study. The samples were analysed by 2D-electrophoresis in order to determine the differential protein expression. The proteins were separated according to the charge in immobilized pH 3-10 gradient strips and then by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Proteins of interest were excised, digested with trypsin and the resulting peptides were separated and identified.

RESULTS: Three differentially expressed apolipoproteins (Apo) were identified based on the protein profile using proteomic techniques: Apo-A1, Apo-A4 and Apo-E. Apo-A4 levels were significantly lower in HCC than in non-HCC patients regardless of etiology (P < 0.01). Multivariate logistic regression showed that Apo-A4 and Apo-A1 were the only independent factors related to HCC diagnosis (P < 0.05). The receiver operating characteristic (ROC) curve including both Apo-A4 and Apo-A1 showed an area under the ROC of 0.944 (P < 0.001), a sensitivity of 0.89 and a specificity of 0.81 for diagnosis of HCC.

CONCLUSION: Apo-A4 and Apo-A1 may be used clinically as biomarkers of HCC with a high sensibility and specificity. These findings may provide additional insights into the mechanism of HCC development and progression.

Keywords: Liver cancer, Apolipoproteins, Serum biomarkers, 2D polyacrylamide gel electrophoresis, Mass spectrometry