title: The role of hepatic expression of STAT1, SOCS3 and PIAS1 in the response of chronic hepatitis C patients to therapy.
abstract: BACKGROUND
  The underlying mechanisms of hepatitis C virus (HCV) resistance to treatment are unknown. Signal transducers and activators of transcription (STAT) proteins play a critical role in antiviral defense.
  
  
  OBJECTIVE
  To explore some of the mechanisms of HCV resistance to interferon, the expression of STAT1 and its negative regulators, protein inhibitor of activated STAT (PIAS1) and suppressor of cytokine signalling (SOCS3), in liver tissues of both inteferon responders and nonresponders in chronic HCV patients.
  
  
  METHODS
  Sixty patients were divided into the following groups: group 1a comprised 38 treatment-responder chronic HCV patients; group 1b consisted of 22 treatment-nonresponder chronic HCV patients; and group 2 consisted of six control subjects. Liver biopsies were examined for histological scoring; STAT1, SOCS3 and PIAS1 expression was analyzed using Western blotting methods.
  
  
  RESULTS
  STAT1 expression in the liver tissue of patients in group 1 was significantly increased compared with group 2 patients (P=0.001), while no significant difference in expression was observed between group 1a and group 1b patients (P=0.747). However, phosphorylated STAT1 protein was expressed at a significantly higher level in liver tissue of patients in group 1a compared with patients in group 1b (P=0.001). Western blot analysis of PIAS1 and SOCS3 protein expression in liver tissues from groups 1 and 2 revealed significantly increased expression in group 1 compared with group 2 (P=0.001). In addition, PIAS1 and SOCS3 protein expression was significantly higher in the liver tissues of patients in group 1b compared with patients in group 1a.
  
  
  CONCLUSIONS
  Levels of STAT1 and⁄or the protein expression of its negative regulators, PIAS1 and SOCS3, may be a good predictor of response to therapy. These could be used as biomarkers that are easily detected by Western blotting or immunostaining during standard histopathological liver biopsy analysis.
authors.forename: Sherif
authors.initials: S
authors.lastname: El-Saadany
authors.forename: Dina H
authors.initials: DH
authors.lastname: Ziada
authors.forename: Hanan
authors.initials: H
authors.lastname: El Bassat
authors.forename: Wael
authors.initials: W
authors.lastname: Farrag
authors.forename: Hesham
authors.initials: H
authors.lastname: El-Serogy
authors.forename: Manal
authors.initials: M
authors.lastname: Eid
authors.forename: Manal
authors.initials: M
authors.lastname: Abdallah
authors.forename: Medhat
authors.initials: M
authors.lastname: Ghazy
authors.forename: Hoda A
authors.initials: HA
authors.lastname: Salem
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology; D001706:Biopsy; D015153:Blotting, Western; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D008099:Liver / Q000821:virology; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011092:Polyethylene Glycols / Q000494:pharmacology; D050828:Protein Inhibitors of Activated STAT / Q000235:genetics*; D011994:Recombinant Proteins / Q000494:pharmacology; D050794:STAT1 Transcription Factor / Q000235:genetics*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; C106529:PIAS1 protein, human; D050828:Protein Inhibitors of Activated STAT; D011994:Recombinant Proteins; C106644:SOCS3 protein, human; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a