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.

Autore Pugliese

• Fimia Gian Maria

Tutti gli autori

• Perdomo A.B. , Ciccosanti F. , Lo Iacono O. , Angeletti C. , Corazzari M. , Daniele N. , Testa A. , Pisa R. , Ippolito G. , Antonucci G. , Fimia G.M. , Piacentini M.

Titolo volume/Rivista

JOURNAL OF PROTEOME RESEARCH

Anno di pubblicazione

2012

ISSN

1535-3907

ISBN

Non Disponibile

Numero di citazioni Wos

16

Ultimo Aggiornamento Citazioni

25/04/2018

Numero di citazioni Scopus

18

Ultimo Aggiornamento Citazioni

26/04/2018

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile