Identification of Circulating Exosomal miR-101 and miR-125b Panel Act as a Potential Biomarker for Hepatocellular Carcinoma.

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with high mortality, and there is an urgent need of new diagnosis measures. This study is aimed at investigating whether circulating exosomal miRNAs could act as biomarkers for the diagnosis of HCC.

Methods: A four-stage strategy was adopted in this study. Candidate miRNA was selected by comprehensive analysis of four GEO datasets and TCGA database. The expression of candidate miRNAs in serum exosomal samples were examined through qRT-PCR. The diagnostic utility of the final validated miRNAs was examined by receiver operating characteristic (ROC) curve analysis.

Results: After synthetical analysis of four GEO datasets, six miRNAs were selected as candidates due to their higher differential fold change. miR-101 and miR-125b were selected as candidate miRNAs to further investigate their potential as biomarkers for HCC due to their differential fold change and their influence on overall survival based on the TCGA database. As a result, miR-101 and miR-125b expressions were remarkably downregulated in both tissues and serum exosomes of patients with HCC. The area under the ROC curves (AUCs) of circulating exosomal miR-101 and miR-125b were 0.894 (95% CI, 0.793-0.994) and 0.812 (95% CI, 0.675-0.950), respectively. The combination of the two miRNAs presented higher diagnostic utility for HCC (AUC = 0.953).

Conclusion: The exosomal miR-101 and miR-125b panel in the serum may act as a noninvasive biomarker for HCC detection.