Circulating Plasma Exosomal MiRNA Profiles Serve As Potential Metastasis-related Biomarkers for Hepatocellular Carcinoma

Exosomes carry functional molecules that can regulate cancer progression. Understanding the function of exosomal markers may provide invaluable insights into the mechanism of metastasis in hepatocellular carcinoma (HCC). The aim of the present study was to identify metastasis-associated microRNAs (miRNAs/miRs) expressed in plasma exosomes. A miRNA microarray and reverse transcription-quantitative PCR were used to analyze the plasma exosome miRNA expression profiles of patients with metastatic or non-metastatic HCC. Receiver operating characteristic (ROC) curve and Kaplan-Meier analyses were used to evaluate the predictive performance and prognostic efficacy of candidate miRNAs identified in the Gene Expression Omnibus database (dataset accession no. GSE67140). Bioinformatics analysis was used to examine the role of exosomal miRNAs in HCC metastasis. A total of 32 miRNAs were differentially expressed in plasma exosomes of patients with metastatic HCC compared with in those of patients with non-metastatic HCC. Additionally, the expression levels of six miRNAs were consistent between plasma exosome samples and matched tissue samples. ROC analysis demonstrated that miR-18a, miR-27a and miR-20b could discriminate metastatic HCC from non-metastatic HCC. Furthermore, the prognostic efficacy of the combination of three miRNAs (miR-18a, miR-20b and miR-221) was superior to that of individual miRNAs. Survival analysis demonstrated that high expression levels of the candidate miRNAs were associated with poor prognosis. Bioinformatics analysis indicated that the potential target genes of these miRNAs were involved in biological processes, molecular functions and cellular components that were associated with metastasis. The present findings suggested that these exosomal miRNAs may serve important roles in HCC lung metastasis and could represent a complementary clinical tool for the assessment of HCC prognosis.