鉴定急性心肌梗死和糖尿病肾病中的共表达中枢基因和转录因子。

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Our study reveals the common pathogenesis of AMI and DN. These common pathways and hub genes may provide new ideas for further mechanistic studies.

背景：急性心肌梗死（AMI）和糖尿病肾病（DN）是常见的临床合并症，但它们的治疗具有挑战性，预后较差。目前尚无关于合并症的生物信息学机制的研究，本研究旨在探讨这种机制。

方法：我们从基因表达综合数据库（GEO）平台下载 AMI 数据（GSE66360）和 DN 数据集（GSE30528 和 GSE30529）。GSE66360 数据集分为训练集和验证集两部分，GSE30529 用作训练集，GSE30528 用作验证集。在确定训练集中 AMI 和 DN 之间的共同差异表达基因（DEGs）后，进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析以及蛋白质-蛋白质相互作用（PPI）网络构建。通过 MCODE 构建子网络图，并通过 Cytohubba 插件筛选 15 个枢纽基因。对筛选出的枢纽基因进行验证，并对筛选出的 15 个枢纽基因进行 GO、KEGG、Gene MANIA 分析和转录因子（TF）预测。最后，我们进行了 TF 差异分析、富集分析以及 TF 和基因调控网络构建。

结果：共鉴定出 46 个基因（43 个上调和 3 个下调）进行后续分析。GO 功能分析强调了基因主要存在于参与抗原加工和呈递、脂肽结合、NAD+核苷酶活性和 Toll 样受体结合的囊泡膜和分泌颗粒膜中。分析的 KEGG 途径主要在吞噬体、中性粒细胞胞外诱捕网形成、自然杀伤细胞介导的细胞毒性、细胞凋亡、FcγR 介导的吞噬作用和 Toll 样受体信号通路中。鉴定并验证了 8 个共表达的枢纽基因，即 TLR2、FCER1G、CD163、CTSS、CLEC4A、IGSF6、NCF2 和 MS4A6A。在 AMI 中鉴定并验证了 3 个转录因子，即 NFKB1、HIF1A 和 SPI1。

结论：本研究揭示了 AMI 和 DN 的共同发病机制。这些共同的途径和枢纽基因可能为进一步的机制研究提供新的思路。