Blood exosomal miRNA profiling reveals the complexity of hepatocellular carcinoma and identifies potential biomarkers as differential diagnosis

Hepatocellular carcinoma (HCC) is one of leading causes of cancer‐related deaths worldwide, but there is a shortage of effective biomarkers for its diagnosis. We aimed to explore exosomal miRNAs as potential biomarkers for HCC diagnosis. After the eliminations, this study included 89 patients from Xiangya Hospital of Central South University between August 2017 and May 2018. The principal component analysis (PCA) analysis suggested that daily alcohol consumption could alter the blood exosomal miRNA profiles of HBV positive non-HCC patients through miR-3168 and miR-223-3p. The miRNA profiles also revealed the tumor stages of HCC patients. High expression of miR-455-5p and miR-30c-5p, which significantly correlated with better overall survival in tumor tissues, could also be detected in blood exosomes. Two pairs of miRNAs (miR-584-5p/miR-106-3p and miR-628-3p/miR-941) showed 94.1% sensitivity and 68.4% specificity to differentiate HCC patients from non-HCC patients. The specificity of the combination was substantially influenced by alcohol consumption habits. This study suggested that blood exosomal miRNAs can be used as new non-invasive diagnostic tools for HCC. However, their accuracy could be affected by tumor stage and alcohol consumption habits.