Abstract

BACKGROUND: Recently, increasing research evidence indicates that miRNA plays important roles in oncogenesis of hepatocellular carcinoma (HCC). The objective of this study was to investigate the potential of plasma miRNAs as biomarkers for HCC determination.

MATERIAL AND METHODS: This trial included 4 phases: (i) miRNAs in tumor tissues were screened with a miRNA array for determining candidate miRNAs. (ii) Candidate miRNAs were measured by RT-qPCR in plasma of 10 HCC patients before and after surgery (7–10 days) for target miRNAs that displayed a pattern of postoperative decrease. (iii) Plasma levels of target miRNAs in 37 HCC patients, 29 cirrhosis patients, and 31 healthy controls were measured by RT-qPCR for determining potential biomarkers. (iv) The powers of biomarkers for differentiating HCC were validated and the correlations with clinicopathological variables of HCC patients were analyzed.

RESULTS: miRNA array demonstrated an abnormal expression of 92 miRNAs in tumor tissues compared to adjacent non-tumor tissues. Of those molecules with an over-expressed level in tumor tissues and preoperative plasmas, a decrease in postoperative plasma was observed in miR-15b-5p, miR-338-5p, and miR-764. Plasma levels of these miRNAs in HCC patients were higher than in the other 2 groups (P<0.05). Receiver-operator characteristic (ROC) curve analyses suggested these plasma miRNAs could be useful biomarkers for determining HCC. miR-338-5p yielded an area under the ROC curve (AUC) of 0.799 (74.5% sensitivity and 82.8% specificity) and 0.909 (72.3% sensitivity and 99.68% specificity) to discriminate HCC patients from cirrhosis patients and healthy controls, respectively. The expression level of miR-338-5p was negatively correlated with the level of AFP (r=–0.306, P=0.036), and the expression level of miR-764 was positively correlated with the tumor size (r=0.371, P=0.01).

CONCLUSIONS: Circulating miR-15b-5p, miR-338-5p, and miR-764 may be biomarkers for diagnosis of HCC.

Keywords: Carcinoma, Hepatocellular - surgery, Biomarkers, Tumor - blood, Case-Control Studies, Gene Expression Profiling, Liver Neoplasms - surgery, MicroRNAs - blood, Postoperative Period, preoperative period