Background/purpose : Exosomal microRNAs (exo-miRs) have been reported to play an important role in cancer metastasis. This study aimed to identify pro-metastatic circulating exo-miRs in hepatocellular carcinoma (HCC).
Methods : NGS-based plasma exo-miR profile was analyzed in 14 patients with HCC, consisted of 8 patients without metastasis and 6 patients with metastasis within 1 year of follow up. Integrative analyses were performed to select candidate miRs using two different public expression datasets-GSE67140 and The Cancer Genomic Atlas Liver Hepatocellular Carcinoma (TCGA_LIHC). Validation was performed in stored blood sample of 150 HCC patients at the time of diagnosis. Downstream signaling pathway of selected miR was predicted by Targetscan and Ingenuity pathway analysis (IPA).
Results : A total of 61 miRs were significantly overexpressed in patients with metastasis. Integrative analyses with public datasets identified 3 of 61 miRs, miR-106b-5p, miR-1307-5p, and miR-340-5p, which commonly overexpressed both in metastasis and vascular invasion group and showed prognostic implication. In validation study, circulating exo-miR-1307-5p was overexpressed in metastasis group (P=0.04). It was also significantly overexpressed in patients with vascular invasion and tumor recurrence. The expression of circulating exo-miR-1307-5p was correlated with the progression of tumor stage (P<0.0001). In a comprehensive bioinformatics analysis, the downstream pathway of miR-1307-5p, which promoting epithelial mesenchymal transmission (EMT), was proposed as a down-regulation of SEC14L2 and ENG.
Conclusion : This study suggested circulating exo-miR-1307-5p as a metastasis driver molecule and a predictive marker for the occurrence of metastasis in HCC patients. SEC14L2 and ENG were predicted as target tumor suppressor gene of miR-1307, which promoting EMT.
