Profiles of differential expression of circulating microRNAs in hepatitis B virus-positive small hepatocellular carcinoma.

BACKGROUND: Abnormally expressed circulating microRNA (miRNA) may serve as a potential biomarker for the diagnosis of cancer patients. OBJECTIVE: We sought to determine the differentially expressed circulating microRNAs in patients with hepatitis B virus (HBV)-positive small hepatocellular carcinoma (HCC) compared to other HBV-positive benign liver diseases. METHODS: The miScript miRNA PCR Array was used to detect the levels of 84 miRNAs in plasma or serum samples of patients with HBV-related small HCC (23 cases), liver cirrhosis (LC) (20 cases), chronic hepatitis B (CHB) (20 cases) and healthy controls (16 cases). MiRNAs with fold-change values 2o r 0.5 compared to healthy controls were considered to be deregulated miRNAs. RESULTS:The results of duplicate plasma experiments were not reliable. Comprehensive analysis of the two serum experiments showed that the quality controls all met the requirements. We found 18 differentially expressed miRNAs. Relative to healthy controls, nine, three, and 11 miRNAs were up-regulated in the CHB group, LC group and small HCC group, respectively. In contrast, one, three, and three miRNAs were down-regulated in the same patient groups, respectively. Interestingly, miR-195, miR-25 and miR-16 were up-regulated, and miR-205 was down-regulated, in all three experimental groups. Moreover, only in the HCC group, miR-18a, miR-100, miR-145 and miR-223 were up-regulated 3.48-, 2.95-, 2.12- and 3.91-fold, respectively, and miR-200a and miR-222 were down-regulated 2.56- and 2.00-fold, respectively. CONCLUSIONS:Our study demonstrated the presence of six differentially expressed serum microRNAs in HBV-positive small HCC compared to other benign liver diseases associated with HBV.