Identification of core genes and pathways between geriatric multimorbidity and renal insufficiency: potential therapeutic agents discovered using bioinformatics analysis

Abstract

Background: Geriatric people are prone to suffer from multiple chronic diseases, which can directly or indirectly affect renal function. Through bioinformatics analysis, this study aimed to identify key genes and pathways associated with renal insufficiency in patients with geriatric multimorbidity and explore potential drugs against renal insufficiency. Methods: The text mining tool Pubmed2Ensembl was used to detect genes associated with the keywords including "Geriatric", "Multimorbidity" and "Renal insufficiency". The GeneCodis program was used to specify Gene Ontology (GO) biological process terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Protein–protein interaction (PPI) networks were constructed using STRING and visualized in Cytoscape. Module analysis was performed using CytoHubba and Molecular Complex Detection (MCODE) plugins. GO and KEGG analysis of gene modules was performed using the Database for Annotation, Visualization and Integrated Discover (DAVID) platform database. Genes clustered in salient modules were selected as core genes. Then, the functions and pathways of core genes were visualized using ClueGO and CluePedia. Finally, the drug-gene interaction database was used to explore drug-gene interactions of the core genes to identify drug candidates for renal insufficiency in patients with geriatric multimorbidity. Results: Through text mining, 351 genes associated with "Geriatric", "Multimorbidity" and "Renal insufficiency" were identified. A PPI network consisting of 216 nodes and 1087 edges was constructed and CytoHubba was used to sequence the genes. Five gene modules were obtained by MCODE analysis. The 26 genes clustered in module1 were selected as core candidate genes primarily associated with renal insufficiency in patients with geriatric multimorbidity. The HIF-1, PI3K-Akt, MAPK, Rap1, and FoxO signaling pathways were enriched. We found that 21 of the 26 selected genes could be targeted by 34 existing drugs. Conclusion: This study indicated that CST3, SERPINA1, FN1, PF4, IGF1, KNG1, IL6, VEGFA, ALB, TIMP1, TGFB1, HGF, SERPINE1, APOA1, APOB, FGF23, EGF, APOE, VWF, TF, CP, GAS6, APP, IGFBP3, P4HB, and SPP1 were key genes potentially involved with renal insufficiency in patients with geriatric multimorbidity. In addition, 34 drugs were identified as potential agents for the treatment and management of renal insufficiency.