Bioinformatic Analysis And Functional Prediction Of Intrahepatic Cholangiocarcinoma Related Genes

Objective:Bioinformatics was used to analyze the differentially expressed genes in intrahepatic cholangiocarcinoma(ICCA),and the function and signal pathway of differentially expressed genes were analyzed,so as to provide a theoretical basis for clinical screening of ICCA related molecular markers and drug targets.Methods:A gene chip(GSE322225)was downloaded from the GEO database that included intrahepatic cholangiocarcinoma tissue and normal paracancer tissue.The dataset included 149 samples of intrahepatic cholangiocarcinoma tissue and 6 samples of paracancer tissue.The differentially expressed genes(DEGs)in ICCA tissues were selected by online analysis with GEO2 R tool.GO enrichment analysis and KEGG signaling pathway analysis were performed on differentially expressed genes using DAVID database,and functional annotation was performed on differentially expressed genes.Based on the STRING database,a protein-protein interaction(PPI)regulatory network was constructed,and MCC algorithm was used to screen the key genes with high connectivity.The expression and prognostic effects of key genes were analyzed by TCGA online software.Results :A total of 209 differentially expressed genes in ICCA were screened,including 149 up-regulated genes and 60 down-regulated genes.GOanalysis showed that the up-regulated differential expression genes mainly involved in the binding of intracellular proteins,the regulation of transcription process and apoptosis.The biological functions of the down-regulated differentially expressed genes mainly involved in biological behaviors of various biological membrane,oxidizing reaction and oxygen-binding processes,and involved in the biotransformation of various endogenous substances(such as arachidonic acid,fatty acids,sterols,etc.)and exogenous substances(carcinogens,drugs,etc.).KEGG analysis showed that the up-regulated genes were mainly involved in biological processes such as PIK-AKT signaling pathway,spliceosome and ECM receptor interaction.The down-regulated genes were mainly involved in the biological metabolism of cytochrome P450,the metabolism of chemical carcinogens and other biological metabolism.Protein-protein interaction PPI network screened 12 key genes,including COL1A2,DHX16,NCOR1,CYP2B6,SMAD3,MRPS5,SF3B2,GABBR1,GART,U2 SURP,CYP2A6 and CYP4A11.The TCGA database verified 12 key genes.The results showed that 8 key genes were highly expressed in HCC tissues,and 4 genes were poorly expressed.Survival analysis showed that only the low expression of CYP2B6 was closely related to poor prognosis.Conclusion:1.The high expression of genes related to PI3K-AKT,spliceosome and ECM receptor pathway may be of certain significance for the pathogenesis of ICCA.2.The low expression of genes related to various biological metabolic pathways such as the biological metabolism of cytochrome P450 and the metabolism of chemical carcinogens may promote the occurrence and development of ICCA.3.SMAD,MRPS5,GART,GRBBP1 and other genes could play a role in the pathogenesis of ICCA.