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

// Xin Guo 1, 2, 3 , Xiaohui Lv 4 , Xing Lv 2 , Yueyun Ma 5 , Lin Chen 1, * and Yong Chen 2, * 1 Department of General Surgery, Chinese PLA General Hospital, Beijing, P.R. China 2 Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, P.R. China 3 Department of Endoscopic Surgery, Chinese PLA 451st Hospital, Xi’an, Shaanxi, P.R. China 4 Department of Gynecology and Obstetrics, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, P.R. China 5 Department of Clinical Laboratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, P.R. China * Authors share co-senior authorship Correspondence to: Yong Chen, email: yongchen62@yahoo.com Lin Chen, email: chenlinbj@sina.com Keywords: miR-21, AFP, hepatocellular carcinoma, ROC, biomarker Received: December 19, 2016      Accepted: March 21, 2017      Published: April 19, 2017 ABSTRACT 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.