Comprehensive analysis of survival related ceRNA regulatory net- work in Cholangiocarcinoma

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Abstract Background: Cholangiocarcinoma (CCA) is a highly malignant disease with poor prognosis. Its occurrence and development mechanisms remain unearthed. The ceRNA network describes the relationship between cancer-related RNAs and reveals the potential regulatory mechanism in CCA pathogenesis. Method: The genome transcriptome dataset of CCA was downloaded from the TCGA database. Differential expressional and survival analysis were performed by "edgeR" and "survival" package in R soft (|logFC|≥2, adjusted P-value<0.05), respectively. The interaction of miRNA-lncRNA and miRNA-mRNA were predicted by the miRanda and TargetScan. The ceRNA networks were visualized by the cytoscape 3.7. The heat maps, PCA analysis, KEGG and GO enrichment analysis, and prognostic model were performed and visualized on the online platform. Result: 6837 DEmRNAs, 2771 DElncRNAs, and 173 DEmiRNAs were screened out and ceRNA was constructed consisting of 434 lncRNA-miRNA pairs and 284 miRNA-mRNA pairs with 200 lncRNAs, 21 miRNAs and 245 mRNAs. Moreover, 3 lncRNAs (AC090772.1, LINC00519 and THAP7-AS1) and their downstream mRNAs (MECOM, MBNL3, RCN2) were significantly related to survival time. Finally, four key networks associated with survival-related DElncRNAs and DEmRNAs (LINC00519/hsa-mir-22/MECOM, THAP7-AS1/hsa-mir-429/MBNL3, THAP7-AS1/hsa-mir-155/MBNL3 and THAP7-AS1/hsa-mir-155/RCN2) were obtained. The disease-specific survival (DSS) prognostic model was established and showed the predictive ability based on these candidate ceRNA networks (AUC=0.66~0.83). Conclusion: The study provided a novel ceRNA network related to survival time that had broaden our understanding of the regulatory mechanisms in the development of CCA, as well as served as potential targets for drug development to improve the prognosis of CCA.

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