title: Liver protein profiling in chronic hepatitis C: identification of potential predictive markers for interferon therapy outcome.
abstract: The current anti-hepatitis C virus (HCV) therapy, based on pegylated-interferon alpha and ribavirin, has limited success rate and is accompanied by several side effects. The aim of this study was to identify protein profiles in pretreatment liver biopsies of HCV patients correlating with the outcome of antiviral therapy. Cytosolic or membrane/organelle-enriched protein extracts from liver biopsies of eight HCV patients were analyzed by two-dimensional fluorescence difference gel electrophoresis and mass spectrometry. Overall, this analysis identified 21 proteins whose expression levels correlate with therapy response. These factors are involved in interferon-mediated antiviral activity, stress response, and energy metabolism. Moreover, we found that post-translational modifications of dihydroxyacetone kinase were also associated with therapy outcome. Differential expression of the five best performing markers (STAT1, Mx1, DD4, DAK, and PD-ECGF) was confirmed by immunoblotting assays in an independent group of HCV patients. Finally, we showed that a prediction model based on the expression levels of these markers classifies responder and nonresponder patients with an accuracy of 85.7%. These results provide evidence that the analysis of pretreatment liver protein profiles is valuable for discriminating between responder and nonresponder HCV patients, and may contribute to reduce the number of nonresponder patients exposed to therapy-associated risks.
authors.affiliation: National Institute for Infectious Diseases IRCCS L. Spallanzani, Rome, Italy.
authors.forename: Ariel Basulto
authors.initials: AB
authors.lastname: Perdomo
authors.forename: Fabiola
authors.initials: F
authors.lastname: Ciccosanti
authors.forename: Oreste Lo
authors.initials: OL
authors.lastname: Iacono
authors.forename: Claudio
authors.initials: C
authors.lastname: Angeletti
authors.forename: Marco
authors.initials: M
authors.lastname: Corazzari
authors.forename: Nicola
authors.initials: N
authors.lastname: Daniele
authors.forename: Angela
authors.initials: A
authors.lastname: Testa
authors.forename: Roberto
authors.initials: R
authors.lastname: Pisa
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ippolito
authors.forename: Giorgio
authors.initials: G
authors.lastname: Antonucci
authors.forename: Gian Maria
authors.initials: GM
authors.lastname: Fimia
authors.forename: Mauro
authors.initials: M
authors.lastname: Piacentini
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D016000:Cluster Analysis; D015180:Electrophoresis, Gel, Two-Dimensional; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D025341:Principal Component Analysis; D011379:Prognosis; D020543:Proteome / Q000032:analysis*; D040901:Proteomics; D011994:Recombinant Proteins / Q000627:therapeutic use; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D016898:Interferon-alpha; D020543:Proteome; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a