Circulating miR-21 serves as a serum biomarker for hepatocellular carcinoma and correlated with distant metastasis.

Serum miRNAs have gained great popularity to act as circulating biomarkers of several cancers. In this study, we aimed to evaluate the diagnostic efficiency of serum miR-21 as novel biomarkers for patients with hepatocellular carcinoma (HCC) and other controls. A total of 533 individuals were recruited and conducted in a two-step analysis. The pilot group included 40 HCC patients and 40 healthy donors. The expression levels of miR-21 were significantly higher in primary HCC tissues than in adjacent noncancerous tissues (P<0.0001). HCC patients exhibited significantly higher serum levels of miR-21 than HD (P<0.0001). In the verification group, the mean serum levels of miR-21 in 175 patients with HCC were significantly higher than in 64 with CHB, 78 with LC and 136 HD (all P<0.0001). ROC curves demonstrated that the AUC of miR-21 was 0.849, sensitivity 82.1% and specificity 83.9%. Furthermore, serum miR-21 maintained its diagnostic efficiency in AFP-negative HCC subgroups with AUC 0.831, sensitivity 81.2% and specificity 83.2%. The serum levels of miR-21 could distinguish HCC from CHB and LC (AUC 0.789, sensitivity 76.9%, specificity 85.7% and AUC 0.814, sensitivity 80.8%, specificity 72.9%, respectively). In addition, the serum levels of miR-21 were significantly associated with clinical stage (P=0.006) and distant metastasis (P=0.000). Thus, our findings suggest that miR-21 together with AFP may help enhance the diagnosis of HCC, especially of AFP-negative HCC, and could distinguish HCC from CHB and LC.