Circulating miR-106b-3p, miR-101-3p and miR-1246 as diagnostic biomarkers of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common liver cancer and second leading cause of cancer related death worldwide. Most HCCs occur in a damaged liver cirrhotic background. No dependable molecular biomarkers exist for the early detection of HCC, one of the reasons of its poor prognosis. MicroRNAs (miRNAs) have attracted attention as potential blood-based biomarkers. To identify circulating miRNAs with diagnostic potential in HCC, based on preliminary RNAseq studies on plasma samples from a small set of HCC patients, cirrhotic patients and healthy controls, we validated 4 miRNAs by the use of droplet digital PCR (ddPCR) in independent plasma and serum cohorts of patients and controls. The analyses established the differential level of miR-101-3p, and miR-106-3p in plasma or serum samples of HCC vs. cirrhotic patients or control subjects. The diagnostic accuracy was measured using ROC curve analyses: a combined classifier consisting of miR-101-3p and miR-106b-3p produced the best diagnostic precision both in plasma and serum. Plasma HCC vs. control exhibited an AUC=0.95 (sensitivity 92.9% and specificity 90.0%); serum HCC vs. cirrhosis exhibited an AUC=0.96 (sensitivity 94.1% and specificity 84.6%). Thus, miR-101-3p/miR-106b-3p two-miRNAs classifier exhibits a considerable clinical value in the diagnosis of HCC, when assayed either in plasma or serum