Survival analysis of genome-wide profiles coupled with Connectivity Map database mining to identify potential therapeutic targets for cholangiocarcinoma.

Abstract

Cholangiocarcinoma (CCA) is one of the most common epithelial cell malignancies worldwide. However, its prognosis is poor. The aim of the present study was to examine the prognostic landscape and potential therapeutic targets for CCA. RNA sequencing data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) dataset and processed. A total of 172 genes that were significantly associated with overall survival of patients with CCA were identified using the univariate Cox regression method. Bioinformatics tools were applied using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO). It was identified that ‘Wnt signaling pathway’, ‘cytoplasm’ and ‘AT DNA binding’ were the three most significant GO categories of CCA survival-associated genes. ‘Transcriptional misregulation in cancer’ was the most significant pathway identified in the KEGG analysis. Using the Drug-Gene Interaction database, a drug-gene interaction network was constructed, and 31 identified genes were involved in it. The most meaningful potential therapeutic targets were selected via protein-protein and gene-drug interactions. Among these genes, polo-like kinase 1 (PLK1) was identified to be a potential target due to its significant upregulation in CCA. To rapidly find molecules that may affect these genes, the Connectivity Map was queried. A series of molecules were selected for their potential anti-CCA functions. 0297417-0002B and tribenoside exhibited the highest connection scores with PLK1 via molecular docking. These findings may offer novel insights into treatment and perspectives on the future innovative treatment of CCA.