ESPRESSIONE'DEI'MICRORNA'MIR221'E'MIR222' NEL'CARCINOMA'EPATOCELLULARE' SIGNIFICATO'CLINICO'E'PROGNOSTICO

Background: Hepatocellular carcinoma (HCC) is a primary cancer of the liver with high incidence and mortality. It is managed with a multidisciplinary approach depending on the stage of disease with a combination of surgical resection, liver transplant, loco-regional therapies and chemotherapy. Several diagnostic and prognostic tools have been investigated to improve outcomes, including biological marker, radiological and histopathological features, but at present there is no univocal consensus on their efficacy. In the era of genomics and molecular medicine, the role of microRNAs is being studied in HCC with the aim to identify a signature of specific microRNAs selectively expressed in HCC to use as diagnostic and prognostic markers as well as possible therapeutic targets. MicroRNA miR-221 and miR-222 may be upregulated in over 80% of HCCs. The aim of this study was to assess miR-221 and miR-222 expression in paired hepatic tumoral and non-tumoral tissues of patients undergoing liver resection for HCC. Primary outcome was the presence of significant upregulation in the tumoral tissue compared to the matched non-tumoral tissue. Secondary outcomes were the correlation of miR-221 and miR-222 expression with clinical variables and survival. Methods: Eligible patients undergoing liver resection for HCC at National Cancer Institute (Milan) were prospectively included in the study. Paired tumoral and non-tumoral hepatic tissues were sampled intraoperatively, fresh-frozen and analyzed for miR-221 and miR-222 expression. Clinical, pathological and survival data were prospectively recorded. Upregulation was deemed significant with a tumoral/non-tumoral ratio >1. Kaplan-Meier curves were used to assess survival. Prognostic efficacy of miR-222 ratio was evaluated by receiver operating curve (ROC) analysis. Results: Between January 2012 and September 2015, 56 patients were enrolled. Six patients were BCLC 0, 35 BCLC A, 12 BCLC B and 3 BCLC C. MiR-221 and miR-222 were upregulated in 59% and 52% of cases, respectively. ...