miRNAs are considered promising non-invasive biomarkers. Serum represents the major source of biomarkers, being readily accessible for many analytical tests. Recently, whole blood has drawn increasing interest in biomarker studies due to the presence of cancer-interacting cells and circulating cancer cells. Although Hepatocellular Carcinoma (HCC) is the seventh most frequent cancer worldwide, fragmented information exists regarding the miRNome characterization in blood and serum. We profiled the circulatory miRNome of paired serum and blood samples from 20 HCC patients, identifying 274 miRNA expressed in serum and 670 in blood, most of them still uncharacterized. 157 miRNA significantly differ between the two biofluids with 28 exclusively expressed in serum. Six miRNA clusters significantly characterize the two compartments, with the cluster containing miR-4484, miR-1281, miR-3178, miR-3613-3p, miR-4532, miR-4668-5p, miR-1825, miR-4487, miR-455-3p, miR-940 having the highest average expression in serum compared to blood. The ontological analysis revealed a role of these miRNAs in cancer progression, vascular invasion and cancer immune surveillance thought the regulation of DUSP1, PD-L1 and MUC1. Taken together, these results provide the most comprehensive contribution to date towards a complete miRNome profile of blood and serum for HCC patients. We show a consistent portion of circulatory miRNAs being still unknown.
