Integrated analysis of competing endogenous RNA network revealing potential prognostic biomarkers of hepatocellular carcinoma

摘要

Objective : The goal of our study is to identify a competing endogenous RNA (ceRNA) network using dysregulated RNAs between HCC tumors and the adjacent normal liver tissues from The Cancer Genome Atlas (TCGA) datasets, and to investigate underlying prognostic indicators in hepatocellular carcinoma (HCC) patients. Methods : All of the RNA- and miRNA-sequencing datasets of HCC were obtained from TCGA, and dysregulated RNAs between HCC tumors and the adjacent normal liver tissues were investigated by DESeq and edgeR algorithm. Survival analysis was used to confirm underlying prognostic indicators. Results : In the present study, we constructed a ceRNA network based on 16 differentially expressed genes (DEGs), 7 differentially expressed microRNAs and 34 differentially expressed long non-coding RNAs (DELs). Among these dysregulated RNAs, three DELs (AP002478.1, HTR2A-AS1, and ERVMER61-1) and six DEGs (enhancer of zeste homolog 2 [ EZH2 ], kinesin family member 23 [ KIF23 ], chromobox 2 [ CBX2 ], centrosomal protein 55 [ CEP55 ], cell division cycle 25A [ CDC25A ], and claspin [ CLSPN ]) were used for construct a prognostic signature for HCC overall survival (OS), and performed well in HCC OS (adjusted P 0.0001, adjusted hazard ratio = 2.761, 95% confidence interval = 1.838-4.147). Comprehensive survival analysis demonstrated that this prognostic signature may be act as an independent prognostic indicator of HCC OS. Functional assessment of these dysregulated DEGs in the ceRNA network and gene set enrichment of this prognostic signature suggest that both were enriched in the biological processes and pathways of the cell cycle, cell division and cell proliferation. Conclusions : Our current study constructed a ceRNA network for HCC, and developed a prognostic signature that may act as an independent indicator for HCC OS.