Identificazione di biomarkers proteomici/trascrittomici predittivi per l’insorgenza di epatocarcinoma in soggetti cirrotici con risposta virologica sostenuta dopo trattamento antivirale per l’infezione da virus dell’epatite C

Direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection results in a sustained viral response (SVR) in over 95% of patients. However, hepatocellular carcinoma (HCC), occurs in 5-7% of cirrhotic patients who achieved SVR during the post-treatment follow-up period and predictive biomarkers have not been completely identified. Aim of this study is to define a proteomic and microRNA (miRNA) transcriptomic profile to identify cirrhotic subjects after DAA therapy having a higher risk of developing HCC. Plasma samples were obtained from 8 cirrhotic subjects with sustained virological response (SVR) after direct-acting antiviral (DAA) treatment for HCV infection who developed HCC 1), and who did not develop HCC after therapy 2). Samples were obtained before starting DAA therapy (T0), at the end of the therapy (EOT), and three months after the end of the therapy (TF). Patients were matched for age, gender, and length of follow-up. MiRNA-sequencing and subsequent bioinformatic analysis were performed from total RNA extracted from plasma samples, while, for what concerns the proteomics analysis, LC-MS was preceded by depletion and fractionation workflows to account for the large dynamic range of plasma proteins. among 794 miRNAs isolated, miR-3908 and let7-5f-5p were tendentially modulated at T0, miR- 326, miR-484 and miR-98-5p were significantly modulated at EOT (p: 0,039), whereas miR-106b-5p and miR130b-3p were significantly modulated at TF (p:0,045). A survey on existing literature of gene targets from HCC patients' tumor tissues and HCC cell lines revealed that some of the identified miRNAs are potentially correlated to HCC progression. The proteomics results are currently undergoing bioinformatics analysis. In conclusion, the observation of significantly modulated miRNAs at the end of therapy and at follow-up deserves further analysis for a basic understanding of mechanisms of HCC progression as well as prognostic biormarkers