Identification of candidate biomarkers for hepatocellular carcinoma in plasma of HCV-infected cirrhotic patients by 2-D DIGE

Authors

  • Gustavo Ferrín,

    Corresponding author
    1. Maimónides Institute for Biomedical Research in Córdoba (IMBIC), Reina Sofía University Hospital, University of Córdoba, Córdoba, Spain
    2. Networked Biomedical Research Center, Hepatic and Digestive Diseases (CIBERehd), Barcelona, Spain
    • Correspondence

      Gustavo Ferrín, Maimónides Institute for Biomedical Research in Córdoba (IMIBIC), Córdoba, Spain

      Tel: +34 957011070

      Fax: +34 957010452

      e-mail: gusfesa@gmail.com.

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  • Isidora Ranchal,

    1. Maimónides Institute for Biomedical Research in Córdoba (IMBIC), Reina Sofía University Hospital, University of Córdoba, Córdoba, Spain
    2. Networked Biomedical Research Center, Hepatic and Digestive Diseases (CIBERehd), Barcelona, Spain
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  • Camilo Llamoza,

    1. Department of Digestive Diseases, Reina Sofía University Hospital, Córdoba, Spain
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  • Manuel L. Rodríguez-Perálvarez,

    1. Department of Digestive Diseases, Reina Sofía University Hospital, Córdoba, Spain
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  • Antonio Romero-Ruiz,

    1. Maimónides Institute for Biomedical Research in Córdoba (IMBIC), Reina Sofía University Hospital, University of Córdoba, Córdoba, Spain
    2. Department of Cell Biology, Physiology and Immunology, Faculty of Medicine, University of Córdoba, Córdoba, Spain
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  • Patricia Aguilar-Melero,

    1. Maimónides Institute for Biomedical Research in Córdoba (IMBIC), Reina Sofía University Hospital, University of Córdoba, Córdoba, Spain
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  • Pedro López-Cillero,

    1. Maimónides Institute for Biomedical Research in Córdoba (IMBIC), Reina Sofía University Hospital, University of Córdoba, Córdoba, Spain
    2. Networked Biomedical Research Center, Hepatic and Digestive Diseases (CIBERehd), Barcelona, Spain
    3. Liver Transplantation Unit, Reina Sofía University Hospital, Córdoba, Spain
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  • Javier Briceño,

    1. Maimónides Institute for Biomedical Research in Córdoba (IMBIC), Reina Sofía University Hospital, University of Córdoba, Córdoba, Spain
    2. Networked Biomedical Research Center, Hepatic and Digestive Diseases (CIBERehd), Barcelona, Spain
    3. Liver Transplantation Unit, Reina Sofía University Hospital, Córdoba, Spain
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  • Jordi Muntané,

    1. Maimónides Institute for Biomedical Research in Córdoba (IMBIC), Reina Sofía University Hospital, University of Córdoba, Córdoba, Spain
    2. Networked Biomedical Research Center, Hepatic and Digestive Diseases (CIBERehd), Barcelona, Spain
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  • José L. Montero-Álvarez,

    1. Maimónides Institute for Biomedical Research in Córdoba (IMBIC), Reina Sofía University Hospital, University of Córdoba, Córdoba, Spain
    2. Networked Biomedical Research Center, Hepatic and Digestive Diseases (CIBERehd), Barcelona, Spain
    3. Department of Digestive Diseases, Reina Sofía University Hospital, Córdoba, Spain
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  • Manuel De la Mata

    1. Maimónides Institute for Biomedical Research in Córdoba (IMBIC), Reina Sofía University Hospital, University of Córdoba, Córdoba, Spain
    2. Networked Biomedical Research Center, Hepatic and Digestive Diseases (CIBERehd), Barcelona, Spain
    3. Department of Digestive Diseases, Reina Sofía University Hospital, Córdoba, Spain
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Abstract

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.

Aim

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.

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