Identification of key genes and pathways in postoperative cognitive dysfunction: Potential therapeutic drugs discovered using bioinformatics analysis

Abstract Background: Postoperative cognitive dysfunction (POCD) is a common complication after general anesthesia surgery, and the mechanism of POCD has not been completely studied yet. We aim to use bioinformatics to identify the potential key genes and pathways involved in the mechanism of POCD and explore the potential targeted drugs to treat POCD.Methods: Genes related to POCD were detected using pubmed2ensemble, then the Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of these genes were annotated and visualized using GENECODIS. A protein‑protein interaction (PPI) network was constructed by STRING and visualized in Cytoscape, and the Molecular Complex Detection (MCODE) was used to classify the candidate gene modules. Candidate genes were further validated again via Metascape and Cluego for a GO enrichment and KEGG pathway analysis. Finally, Drug-Gene Interaction Database (DGIDB) was used to identify the related drugs.Results: We identified 70 genes related to POCD and as follows 48 candidate genes were obtained following GO and KEGG enrichment analysis. 39 genes were obtained from a PPI network and one gene module including 12 crucial genes were obtained using the MCODE. Lastly, 5 genes including ACE, IL6, TNF, CCL2, CXCL8 related to 3 main signaling pathways---- hypertrophic cardiomyopathy, viral protein interaction with cytokine and cytokine receptor, and IL17 signaling pathway. Furthmore,26 targeted drugs were explored as potential therapeutic agents. Conclusion: In this study, we ultimately identified 5 target genes targetable by 26 drugs for POCD, related to 3 main signaling pathways.