Dysregulated microRNAs with prognostic significance in human hepatocellular carcinoma: a study based on high-throughput microarray

Hepatocellular carcinoma (HCC) is the fifth most widespread type of malignancies with only 18% of postoperative 5-year survival. However, the prognostic value of microRNAs (miRNAs) for HCC has not been fully studied. In this study, we aimed to identify the potential candidates of dysregulated miRNAs for HCC prognosis in the profiling studies based on high-throughput microarray. The literature and NCBI Gene Expression Omnibus (GEO) database were used to identify HCC-related miRNAs. Based on the ranking results of a vote-strategy method, the most constantly stated dysregulated miRNAs were chosen as the predictive biomarkers for HCC patients' survival. For meta-analysis on prognosis, eligible studies were searched and sufficient data were collected adequately. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to estimate the effect size. The top six upregulated and six downregulated miRNAs were identified based on 43 published miRNA profiling studies. Additional 30 studies involving 2735 HCC patients with follow-up data were also included. Among the top 12 dysregulated miRNAs, miR-222, miR-25, miR-221, miR-21, miR-214, miR-199a-3p and miR-199a-5p were closely associated with HCC patients' survival. Both univariate and multivariate results suggested that the low quality of life for HCC patients was significantly related with high miR-21, miR-221, miR-25 and low miR-199a-3p, miR-214. In conclusion, miR-222, miR-221, miR-21 and miR-25 were significantly related with dismal prognosis for HCC patients, and miR-199a-3p and miR-214 emerged as significant predictors of unfavorable prognosis for HCC patients. These miRNAs may serve as potential candidates for HCC prognosis and therapy.