title: Plasma protein biomarkers of hepatocellular carcinoma in HCV-infected alcoholic patients with cirrhosis.
abstract: Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers in the world, with limited options for treatment unless timely diagnosed. Chronic hepatitis C virus (HCV) infection and persistent heavy alcohol consumption are independent risk factors for HCC development, which may induce a specific protein expression pattern different from those caused separately. The aim of the study was to identify protein biomarkers for the detection of HCC in HCV-infected alcoholic patients with cirrhosis in order to improve survival. We compared protein expression profiles of plasma samples from 52 HCV-infected alcoholic patients with and without HCC, using 2-D DIGE coupled with MALDI-TOF/TOF mass spectrometry. The 2-D DIGE results were analyzed statistically using Decyder software, and verified by western-blot and ELISA. In plasma samples from HCV-infected alcoholic patients, we found significantly differential expression profiles of carboxypeptidase-N, ceruloplasmin (CP), complement component 4a (C4a), fibrinogen-alpha (FGA), immunoglobulin mu chain C region, serum albumin, and serum paraoxonase/arylesterase 1 (PON1). Deregulation of plasma/serum levels of the identified proteins was associated to HCV, ethanol consumption, and/or HCC progression. In the validation through ELISA, C4a serum concentration was increased in HCC patients (2.4±1 ng/mg vs 1.8±0.6 ng/mg; p = 0.029), being the only independent predictor of HCC in the multivariate analysis (OR = 2.15; p = 0.015), with an AUROC = 0.70. The combination of C4a, FGA, CP and PON1 improved slightly the predictive ability of C4a alone (AUROC 0.81). In conclusion, we identified proteins related to acute-phase response, oxidative stress, or immune response, whose differential expression in plasma may be attributed to the presence of HCC. Among them, C4a, and its combination with CP, FGA and PON1, could be considered as potentially reliable biomarkers for the detection of HCC in HCV-infected alcoholic patients.
authors: Maimónides Institute for Biomedical Research in Córdoba (IMBIC), Reina Sofía University Hospital, Córdoba, Spain; Biomedical Research Centre Network, Digestive and Liver Diseases (CIBERehd), Córdoba, Spain.
authors: Gustavo
authors: G
authors: Ferrín
authors: Maimónides Institute for Biomedical Research in Córdoba (IMBIC), Reina Sofía University Hospital, Córdoba, Spain; Biomedical Research Centre Network, Digestive and Liver Diseases (CIBERehd), Córdoba, Spain; Hepatology and Liver Transplantation Unit, Reina Sofía University Hospital, Córdoba, Spain.
authors: Manuel
authors: M
authors: Rodríguez-Perálvarez
authors: Maimónides Institute for Biomedical Research in Córdoba (IMBIC), Reina Sofía University Hospital, Córdoba, Spain.
authors: Patricia
authors: P
authors: Aguilar-Melero
authors: Maimónides Institute for Biomedical Research in Córdoba (IMBIC), Reina Sofía University Hospital, Córdoba, Spain; Biomedical Research Centre Network, Digestive and Liver Diseases (CIBERehd), Córdoba, Spain.
authors: Isidora
authors: I
authors: Ranchal
authors: Hepatology and Liver Transplantation Unit, Reina Sofía University Hospital, Córdoba, Spain.
authors: Camilo
authors: C
authors: Llamoza
authors: Maimónides Institute for Biomedical Research in Córdoba (IMBIC), Reina Sofía University Hospital, Córdoba, Spain.
authors: Clara I
authors: CI
authors: Linares
authors: Maimónides Institute for Biomedical Research in Córdoba (IMBIC), Reina Sofía University Hospital, Córdoba, Spain.
authors: Sandra
authors: S
authors: González-Rubio
authors: Maimónides Institute for Biomedical Research in Córdoba (IMBIC), Reina Sofía University Hospital, Córdoba, Spain; Biomedical Research Centre Network, Digestive and Liver Diseases (CIBERehd), Córdoba, Spain.
authors: Jordi
authors: J
authors: Muntané
authors: Maimónides Institute for Biomedical Research in Córdoba (IMBIC), Reina Sofía University Hospital, Córdoba, Spain; Biomedical Research Centre Network, Digestive and Liver Diseases (CIBERehd), Córdoba, Spain; Hepatology and Liver Transplantation Unit, Reina Sofía University Hospital, Córdoba, Spain.
authors: Javier
authors: J
authors: Briceño
authors: Maimónides Institute for Biomedical Research in Córdoba (IMBIC), Reina Sofía University Hospital, Córdoba, Spain; Biomedical Research Centre Network, Digestive and Liver Diseases (CIBERehd), Córdoba, Spain; Hepatology and Liver Transplantation Unit, Reina Sofía University Hospital, Córdoba, Spain.
authors: Pedro
authors: P
authors: López-Cillero
authors: Maimónides Institute for Biomedical Research in Córdoba (IMBIC), Reina Sofía University Hospital, Córdoba, Spain; Biomedical Research Centre Network, Digestive and Liver Diseases (CIBERehd), Córdoba, Spain; Hepatology and Liver Transplantation Unit, Reina Sofía University Hospital, Córdoba, Spain.
authors: José Luis
authors: JL
authors: Montero-Álvarez
authors: Maimónides Institute for Biomedical Research in Córdoba (IMBIC), Reina Sofía University Hospital, Córdoba, Spain; Biomedical Research Centre Network, Digestive and Liver Diseases (CIBERehd), Córdoba, Spain; Hepatology and Liver Transplantation Unit, Reina Sofía University Hospital, Córdoba, Spain.
authors: Manuel
authors: M
authors: de la Mata
mesh_terms: D000437:Alcoholism / Q000150:complications*; D014408:Biomarkers, Tumor / Q000097:blood*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000175:diagnosis*; D004797:Enzyme-Linked Immunosorbent Assay; D006526:Hepatitis C / Q000097:blood / Q000150:complications*; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000209:etiology*; D008113:Liver Neoplasms / Q000097:blood / Q000175:diagnosis*; D012984:Software
chemical_list: D014408:Biomarkers, Tumor