Identification of prognostic factors for intrahepatic cholangiocarcinoma using long non-coding RNAs-associated ceRNA network

Abstract

Background: Accumulating amount of evidence has highlighted the important roles of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in tumor pathogenesis. However, the roles of long non coding RNAs (lncRNAs) in the lncRNA-related ceRNA network of intrahepatic cholangiocarcinoma (ICC) still remain enigmatic. The current study aims to identify prognostic factors in the lncRNA-related ceRNA network of ICC. Methods: The transcriptome sequencing data of lncRNAs, messenger RNA (mRNA) and microRNA (miR) were downloaded from the SRA and TCGA databases. Differentially expressed lncRNAs (DElncRNAs), DEmiRs and DEmRNAs were identified and adopted to construct an lncRNA-miR-mRNA ceRNA network. ICC-associated DEmRNAs were adopted to construct the protein-protein interaction (PPI) network. The expression of the top 6 genes in the hub module was validated with mRNA transcriptome sequencing data and ICC-related gene expression dataset GSE45001, followed by GO and KEGG pathway enrichment analysis. The relationship between the hub gene-associated ceRNA network and the overall survival of patients with ICC was predicted by conducting a Kaplan-Meier survival analysis. Results: Sixty co-expressed DEmRNAs were identified in the ceRNA network. The top 6 hub genes consisted of downregulated FOS, IGF2, FOXO1 and NTF3, upregulated IGF1R, and insignificantly downregulated HGF in ICC tissues, when compared to that of normal adjacent tissues, followed by the successful construction of lncRNA-miR-hub network consisting of 86 ceRNA modules. MME-AS1 and hsa-miR-182 were associated with overall survival in ICC patients. FOS, IGF1R, IGF2, FOXO1, and NTF3 might target "TGF-β signaling pathway", "the hedgehog signaling pathway", "retinol metabolism", or "type II diabetes mellitus"pathways respectively. Conclusion: These results indicate that FOS, IGF1R, IGF2, FOXO1, and NTF3 were useful prognostic factors in determining the prognosis of patients with ICC.