Objective        To investigate the plasma circulating miRNAs as potential biomarkers for screening hepatocellular carcinoma (HCC).       Methods        This study was divided into 4 phases. Firstly

a miRNA array was used to screen miRNAs with abnormal expression in HCC tissues for selecting candidate miRNAs. Secondly

the preoperative and postoperative (7-10 d after surgery) plasma samples of 13 patients with HCC were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR)

and the candidate miRNAs with down-regulated expression after surgery were selected as target miRNAs for further study. Thirdly

the expression profiles of the target miRNAs in the plasma of 39 HCC patients

32 cirrhosis patients and 25 healthy controls were measured by qRT-PCR

and the miRNAs with significant abnormal expressions were determined as potential biomarkers. Finally

the values of the potential biomarkers in diagnosing HCC were analyzed

and their relationship with clinicopathologic parameters were validated.       Results        The expression levels of 40 miRNAs were up-regulated and 52 miRNAs were down-regulated in the tumor tissues. miR-15b-5p and miR-338-5p were significantly over-expressed in the tumor tissues compared with the adjacent non-tumor tissues. According to the reports

miR-15b-5p

miR-338-5p and miR-21-5p were chosen as candidate miRNAs finally. Next

the levels of 3 miRNAs were reduced after surgery. Moreover

higher expression was observed in the plasma of HCC patients than of the cirrhosis patients and healthy controls. Receiver operating characteristic curve (ROC curve) analyses suggested that these plasma miRNAs could be useful biomarkers for discriminating patients with HCC from cirrhosis patients and healthy controls. Especially

miR-338-5p yielded the receiver-operator characteristic area under the curve (AUC) of 0.7624 (sensitivity 64.10% and specificity 87.50%) in discriminating patients with HCC from cirrhosis patients and 0.9046 (sensitivity 89.74% and specificity 84.00%) in discriminating HCC patients from healthy controls. The combination of miR-21-5p and miR-338-5p yielded the specificity of 92.98% in determining HCC from all cases. Moreover

the miRNAs had high sensitivity for HCC diagnosis even to α-fetoprotein (AFP)-negative HCC patients. Further analyses indicated that the expression level of miR-338-5p was negatively correlated with the AFP level (r=-0.344

P=0.032).       Conclusion      Circulating miR-338-5p

miR-21-5p and miR-15b-5p may serve as the potential biomarkers for screening HCC.