Hepatic expression of STAT1, SOCS3 & PIAS1 in HCV Patients and their Role in Response to therapy (original) (raw)

Background/Aim: The underlying mechanisms of HCV resistance to treatment are unknown. STATs play a critical role in antiviral defense. To explore some of the mechanisms of HCV resistance to IFN, we investigated the expression of signal transducer and activator of transcription (STAT1) and its negative regulators protein inhibitor of activated STATs (PIAS1) and suppressor of cytokine signaling (SOCS3) in liver tissues of both IFN responders and non-responders chronic HCV patients. Patients & Methods: 60 patients divided in to group 1a: 38 treatment responder Chronic HCV, group 1b: 22 treatment non-responder chronic HCV patients & control group: 6 subjects. Liver biopsies were taken from them and examined for histological scoring & Western blot analysis of STAT1, SOCS3, and PIAS1 expression. Results: STAT1 expression was significantly increased in liver tissue from group 1 compared to group 2 (P = 0.001), while a none significant difference was observed between group 1a & group 1b (P = 0.747), but phosphorylated STAT1 protein was expressed at a significantly higher level in liver tissue of group 1a compared to group 1b (P = 0.001). Western blotting of PIAS1 and SOCS3 protein expression in liver tissues from group1 & 2 revealed significantly increased expression in group 1 compared to group 2 (P = 0.001). In addition comparing liver tissue from group 1a & group 1b showed that PIAS1 and SOCS3 protein expression was significantly higher in liver of group 1b. Conclusion: Assay for phosphorylated STAT1 and/or its negative regulators, PIAS1 and SOCS3 proteins expression could be a good predictor of response to therapy and these could be used as biomarkers that can be easily detected by western blotting or immune-staining during standard histopathological liver biopsy analysis. Key words: SOCS3, PIAS1, STAT1, HCV, chronic hepatitis c, HCV Therapy Response, IFN, IFN therapy.