Serum miR-224 as a biomarker for detection of hepatocellular carcinoma at early stage.

BACKGROUND AND OBJECTIVE: Circulating microRNAs (miRNAs) are known as potential noninvasive biomarkers for cancers. Overexpression of mircoRNA-224 (miR-224) has been reported in hepatocellular carcinoma (HCC), so the aim of this study was to determine the value of serum miR-224 in diagnosis of HCC at early stage.

METHODS: Three hundred and thirty-five subjects including early-stage HCC, liver cirrhosis (LC), chronic hepatitis B (CHB) and healthy controls (HC) were enrolled in two cohorts. Association of miR-224 expression with HCC was analyzed. The area under curves (AUC) was calculated for miR-224 and compared with that for AFP in detection of HCC at early stage.

RESULTS: Our results demonstrated that serum miR-224 was significantly higher in early-stage HCC than that in LC, CHB and HC, respectively. Besides, it decreased significantly after surgery in early-stage HCC, and there was a positive correlation between miR-224 in sera and that in paired tumor tissues. Serum miR-224 levels also showed a significant correlation with BCLC stages of HCC. Expression of miR-224 was significantly higher in tumorous tissues than that in adjacent non-tumorous tissues of HCC, pathologic liver tissues of LC and CHB. Further, ROC analysis demonstrated that AUC were 0.880 (95% CI: 0.838-0.923; sensitivity: 86.5%, specificity: 76.7%) for serum miR-224 in discriminating early-stage HCC from all three controls (LC, CHB and healthy subjects), higher than that for AFP (AUC: 0.700, 95% CI: 0.633-0.767; sensitivity: 71.9%, specificity: 63.7%) (P<0.01). Moreover, serum miR-224 also had a better performance than AFP in discriminating HCC from each of the three control groups. When miR-224 and AFP were used together, the diagnostic accuracy increased significantly compared with either marker alone.

CONCLUSION: These results indicate that serum miR-224 is a potential reliable biomarker in detecting early-stage HCC, with better performance than AFP.