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

Abstract

Background Accumulating evidence has highlighted the important roles of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in tumor biology. However, the roles of cancer long non coding RNAs (lncRNAs) in lncRNA-related ceRNA network of intrahepatic cholangiocarcinoma (ICC) remain enigmatic. The current study aims to identify prognostic factors in the lncRNA-related ceRNA network of ICC. Methods The transcriptome sequencing data of the lncRNAs, messenger RNA (mRNA) and microRNA (miR) were downloaded from SRA, and TCGA database respectively. Differentially expressed lncRNAs (DElncRNAs), DEmiRs and DEmRNAs were identified and adopted to construct lncRNA-miR-mRNA ceRNA network. ICC-associated DEmRNAs were adopted to construct the PPI network. The expression of the top 6 genes in the hub module was validated in mRNA transcriptome sequencing data and ICC-related gene expression dataset GSE45001, followed by GO and KEGG pathway enrichment analysis. The potential function of genes in hub module in the ceRNA network was finally subjected to GSEA. Results Sixty coexpression DEmRNAs were identified in the ceRNA network. The 6 top genes in the hub module consists of FOS, HGF, IGF2, FOXO1, NTF3 (downregulated), and IGF1R (upregulated) in ICC tissues compared to normal adjacent tissues, followed by the successful construction of lncRNA-miR-hub network with 86 ceRNA modules. FOS, IGF2 or IGF1R might regulate the development of ICC by targeting “N-glycan biosynthesis”, “α-linolenic acid metabolism” or “type II diabetes” pathways respectively. Conclusion These results show FOS, IGF2 and IGF1R serve as prognostic factors of ICC patients.