Identification of co-expressed central genes and transcription factors in acute myocardial infarction and diabetic nephropathy

• Published in: BMC medical genomics 2024-05, Vol.17 (1), p.134-134, Article 134
• Main Authors: Li, Bo, Zhao, Xu, Xie, Wanrun, Hong, Zhenzhen, Cao, Ye, Zhang, Yi, Ding, Yan
• Format: Article
• Language: English
• Subjects: Acute myocardial infarction; Analysis; Antigen presentation; Antigen processing; Apoptosis; Bioinformatics; Care and treatment; CD163 antigen; Comorbidity; Complications and side effects; Computational Biology - methods; Cytotoxicity; Databases, Genetic; Datasets; Diabetes; Diabetes mellitus; Diabetic nephropathies; Diabetic Nephropathies - genetics; Diabetic nephropathy; Differentially expressed genes; Disease; DNA binding proteins; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Gene Ontology; Gene Regulatory Networks; Genes; Genetic aspects; Genomics; Heart attack; Heart attacks; Hub genes; Humans; Killer cells; Leukocytes (neutrophilic); Myocardial infarction; Myocardial Infarction - genetics; Natural killer cells; Nephropathy; Phagocytosis; Prevention; Protein Interaction Maps; Protein-protein interactions; Raltegravir; Risk factors; TLR2 protein; Toll-like receptors; Transcription factor; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; Visualization
• ISSN: 1755-8794; 1755-8794
• DOI: 10.1186/s12920-024-01906-7

Acute myocardial infarction (AMI) and diabetic nephropathy (DN) are common clinical co-morbidities, but they are challenging to manage and have poor prognoses. There is no research on the bioinformatics mechanisms of comorbidity, and this study aims to investigate such mechanisms. We downloaded the AMI data (GSE66360) and DN datasets (GSE30528 and GSE30529) from the Gene Expression Omnibus (GEO) platform. The GSE66360 dataset was divided into two parts: the training set and the validation set, and GSE30529 was used as the training set and GSE30528 as the validation set. After identifying the common differentially expressed genes (DEGs) in AMI and DN in the training set, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and protein-protein interaction (PPI) network construction were performed. A sub-network graph was constructed by MCODE, and 15 hub genes were screened by the Cytohubba plugin. The screened hub genes were validated, and the 15 screened hub genes were subjected to GO, KEGG, Gene MANIA analysis, and transcription factor (TF) prediction. Finally, we performed TF differential analysis, enrichment analysis, and TF and gene regulatory network construction. A total of 46 genes (43 up-regulated and 3 down-regulated) were identified for subsequent analysis. GO functional analysis emphasized the presence of genes mainly in the vesicle membrane and secretory granule membrane involved in antigen processing and presentation, lipopeptide binding, NAD + nucleosidase activity, and Toll-like receptor binding. The KEGG pathways analyzed were mainly in the phagosome, neutrophil extracellular trap formation, natural killer cell-mediated cytotoxicity, apoptosis, Fc gamma R-mediated phagocytosis, and Toll-like receptor signaling pathways. Eight co-expressed hub genes were identified and validated, namely TLR2, FCER1G, CD163, CTSS, CLEC4A, IGSF6, NCF2, and MS4A6A. Three transcription factors were identified and validated in AMI, namely NFKB1, HIF1A, and SPI1. Our study reveals the common pathogenesis of AMI and DN. These common pathways and hub genes may provide new ideas for further mechanistic studies.