Expression of the microRNA-143/145 cluster is decreased in hepatitis B virus-associated hepatocellular carcinoma and may serve as a biomarker for tumorigenesis in patients with chronic hepatitis B

摘要

The aims of the present study were to identify the expression profile of microRNA (miR)-143/145 in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC), explore its association with prognosis and investigate whether the serum miR-143/145 expression levels may serve as a diagnostic indicator of HBV-associated HCC. The microRNA (miRNA) chromatin immunoprecipitation dataset was obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus databases, and analyzed using the Wilcoxon signed-rank test. It was observed that the expression of miR-143 and miR-145 was decreased 1.5-fold in HBV-associated HCC samples compared with non-tumor tissue in the TCGA and the datasets (P<0.01). Using the reverse transcription-quantitative polymerase chain reaction, it was further confirmed that miR-143/145 and their host gene MIR143HG were downregulated in HBV-associated HCC tissues compared with corresponding distal non-tumor tissues. The lower level of miR-143 and miR-145 expression was associated with tumor differentiation, and may thus be responsible for a poor prognosis of patients with HBV-associated HCC. The receiver-operating characteristic (ROC) curves were used to explore the potential value of miR-143 and miR-145 as biomarkers for predicting HBV-associated HCC tumorigenesis. In serum, miR-143/145 were identified to be significantly decreased in patients with HBV-associated HCC compared with negative control patients, and their associated areas under the ROC curves were calculated at 0.813 and 0.852 (P<0.05), with each having a sensitivity and a specificity close to 0.80. These results indicated that the decreased expression of the miR-143/145 cluster and their host gene MIR143HG in HBV-associated HCC tissue was associated with prognosis, and each of these miRNAs may serve as a valuable diagnostic biomarker for predicting HBV-associated HCC tumorigenesis.