Hepatocellular carcinoma (HCC) is the most common
liver cancer and second leading cause of
cancer related death worldwide. Most HCCs occur in a damaged cirrhotic background and it may be difficult to discriminate between regenerative nodules and early HCCs. No dependable molecular
biomarker exists for the early detection of HCC.
MicroRNAs (
miRNAs) have attracted attention as potential blood-based
biomarkers. To identify circulating
miRNAs with diagnostic potential in HCC, we performed preliminary RNAseq studies on plasma samples from a small set of HCC patients, cirrhotic patients and healthy controls. Then, out of the identified
miRNAs, we investigated miR-101-3p, miR-106b-3p, miR-1246 and miR-411-5p in plasma of independent HCC patients' cohorts. The use of droplet digital PCR (ddPCR) confirmed the aberrant levels of these
miRNAs. The diagnostic performances of each
miRNA and their combinations were measured using Receiver Operating Characteristic (ROC) curve analyses: a classifier consisting of miR-101-3p, miR-1246 and miR-106b-3p produced the best diagnostic precision in plasma of HCC vs. cirrhotic patients (AUC = 0.99). A similar performance was found when the levels of
miRNAs of HCC patients were compared to healthy controls (AUC = 1.00). We extended the analyses of the same
miRNAs to serum samples. In serum of HCC vs. cirrhotic patients, the combination of miR-101-3p and miR-106b-3p exhibited the best diagnostic accuracy with an AUC = 0.96. Thus, circulating miR-101-3p, miR-106b-3p and miR-1246, either individually or in combination, exhibit a considerable potential value as diagnostic
biomarkers of HCC.