Identification of potential prognostic microRNA biomarkers for predicting survival in patients with hepatocellular carcinoma

Xiwen Liao,1 Guangzhi Zhu,1 Rui Huang,2 Chengkun Yang,1 Xiangkun Wang,1 Ketuan Huang,1 Tingdong Yu,1 Chuangye Han,1 Hao Su,1 Tao Peng1 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China Background: The aim of the present study was to identify potential prognostic microRNA (miRNA) biomarkers for hepatocellular carcinoma (HCC) prognosis prediction based on a dataset from The Cancer Genome Atlas (TCGA). Materials and methods: A miRNA sequencing dataset and corresponding clinical parameters of HCC were obtained from TCGA. Genome-wide univariate Cox regression analysis was used to screen prognostic differentially expressed miRNAs (DEMs), and multivariable Cox regression analysis was used for prognostic signature construction. Comprehensive survival analysis was performed to evaluate the prognostic value of the prognostic signature. Results: Five miRNAs were regarded as prognostic DEMs and used for prognostic signature construction. The five-DEM prognostic signature performed well in prognosis prediction (adjusted P < 0.0001, adjusted hazard ratio = 2.249, 95% confidence interval =1.491–3.394), and time-dependent receiver–operating characteristic (ROC) analysis showed an area under the curve (AUC) of 0.765, 0.745, 0.725, and 0.687 for 1-, 2-, 3-, and 5-year HCC overall survival (OS) prediction, respectively. Comprehensive survival analysis of the prognostic signature suggests that the risk score model could serve as an independent factor of HCC and perform better in prognosis prediction than other traditional clinical indicators. Functional assessment of the target genes of hsa-mir-139 and hsa-mir-5003 indicates that they were significantly enriched in multiple biological processes and pathways, including cell proliferation and cell migration regulation, pathways in cancer, and the cyclic adenosine monophosphate (cAMP) signaling pathway. Conclusion: Our study indicates that the novel miRNA expression signature may be a potential prognostic biomarker for HCC patients. Keywords: miRNA, TCGA, hepatocellular carcinoma, prognosis, biomarker