Exosomal MicroRNAs as Liquid Biopsy Biomarkers in Hepatocellular Carcinoma

PURPOSE: Hepatocellular carcinoma (HCC) has a high incidence in China and exploring effective ways for early diagnosis is an important method to improve the prognosis of patients with HCC. Additional studies reported that. Some kinds of microRNA (miRNA) in plasma will change accordingly during HCC progress, and this change can be used to diagnose HCC, especially with miRNA-122, miRNA-21 and miRNA-96. We were aiming at investigating the values of the exosomal miRNAs in diagnosis and prognosis for HCC patients. PATIENTS AND METHODS: Blood samples from 50 patients with HCC and 50 patients with hepatic cirrhosis and 50 healthy volunteers were obtained. The diagnostic accuracy of the plasma and exosomal miRNAs and the comparisons among different groups were measured by the area under the curve (AUC) on receiver operating characteristic (ROC) curve analysis. RESULTS: Expression levels of miRNA-21 and miRNA-96 were significantly higher in patients with HCC and of miRNA-122 were significantly lower in HCC compared with cirrhotic patients in both exosomes and plasma. Among different groups, exosomal miRNA-122, miRNA-21 and miRNA-96 were significantly more accurate in diagnosing HCC than those miRNAs in plasma and the alpha-fetoprotein (AFP) level. The miRNA panel had high accuracy in discriminating HCC from the cirrhosis group (AUC 0.924; 95% CI; sensitivity 82%, specificity 92%) and healthy volunteers’ group. Exosomal miRNA-21 and miRNA-96 with low expression and miRNA-122 with high expression could be associated with a patient’s survival time. However, the miRNA panel could better predict the HCC patient’s survival time compared with each miRNA individually. CONCLUSION: This study showed that the expression levels of miRNA-122, miRNA-21 and miRNA-96 in exosomes were more significantly changed than those miRNAs in plasma in patients with HCC compared with cirrhotic patients, and the exosomal miRNA panel containing miRNA-122, miRNA-21 and miRNA-96 could be defined as a diagnostic biomarker for patients with HCC. We also conclude that different expression of exosomal miRNAs, especially the miRNA panel, could predict the HCC patient’s prognosis.