Identification and analysis of key genes associated with acute myocardial infarction by integrated bioinformatics methods.

Identification and analysis of key genes associated with acute myocardial infarction by integrated bioinformatics methods.
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DOI:
10.1097/md.0000000000025553
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发表时间:
2021-04-16
期刊:
影响因子:
1.6
通讯作者:
Wang H
Wang H
中科院分区:
医学4区
文献类型:
--
作者:
Guo S;Wu J;Zhou W;Liu X;Liu Y;Zhang J;Jia S;Li J;Wang H

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急性心肌梗死(AMI)是世界范围内严重威胁人类健康的常见病、多发病。本研究旨在通过整合生物信息学工具,探索AMI新的生物标志物和潜在的治疗靶点。基因表达Omnibus(GEO)数据库用于获得AMI和非AMI全血的基因数据。利用R3.6.1软件中的“Limma”软件包筛选差异表达基因(DEG)。通过R 3.6.1软件中的“Bioconductor”和“GOplot”包进行DEG的功能和途径富集分析。为了筛选中心DEG,应用STRING版本11.0数据库、Cytoscape和分子复合物检测(MCODE)。使用Pearson相关性分析评估中心DEG之间的相关性。通过DEG分析,从GSE 66360中分别成功鉴定出289个上调的DEG和62个下调的DEG。主要集中在中性粒细胞活化、免疫反应、细胞因子、核因子-κ B(NF-κB)信号通路、IL-17信号通路和肿瘤坏死因子(TNF)信号通路方面。根据蛋白质相互作用(PPI)数据,排名前10位的枢纽基因包括白细胞介素-8(CXCL 8)、肿瘤坏死因子(TNF)、N-甲酰肽受体2(FPR 2)、生长调节α蛋白(CXCL 1)、转录因子AP-1(JUN)、白细胞介素-1 β(IL 1B)、血小板碱性蛋白(PPBP)、基质金属蛋白酶-9(MMP 9)、toll样受体2(TLR 2)、和高亲和力免疫球蛋白α受体γ亚基(FCER 1G)。相关性分析结果表明,10个中心区DEG之间存在正相关关系。本研究确定了10个DEG作为AMI患者潜在的候选诊断生物标志物。然而,需要进一步的实验来确认与AMI相关的功能通路和枢纽基因。
Acute myocardial infarction (AMI) is a common disease leading threat to human health around the world. Here we aimed to explore new biomarkers and potential therapeutic targets in AMI through adopting integrated bioinformatics tools. The gene expression Omnibus (GEO) database was used to obtain genes data of AMI and no-AMI whole blood. Furthermore, differentially expressed genes (DEGs) were screened using the “Limma” package in R 3.6.1 software. Functional and pathway enrichment analyses of DEGs were performed via “Bioconductor” and “GOplot” package in R 3.6.1 software. In order to screen hub DEGs, the STRING version 11.0 database, Cytoscape and molecular complex detection (MCODE) were applied. Correlation among the hub DEGs was evaluated using Pearson's correlation analysis. By performing DEGs analysis, 289 upregulated and 62 downregulated DEGs were successfully identified from GSE66360, respectively. And they were mainly enriched in the terms of neutrophil activation, immune response, cytokine, nuclear factor kappa-B (NF-κB) signaling pathway, IL-17 signaling pathway, and tumor necrosis factor (TNF) signaling pathway. Based on the data of protein–protein interaction (PPI), the top 10 hub genes were ranked, including interleukin-8 (CXCL8), TNF, N-formyl peptide receptor 2 (FPR2), growth-regulated alpha protein (CXCL1), transcription factor AP-1 (JUN), interleukin-1 beta (IL1B), platelet basic protein (PPBP), matrix metalloproteinase-9 (MMP9), toll-like receptor 2 (TLR2), and high affinity immunoglobulin epsilon receptor subunit gamma (FCER1G). What's more, the results of correlation analysis demonstrated that there was positive correlation between the 10 hub DEGs. Ten DEGs were identified as potential candidate diagnostic biomarkers for patients with AMI in present study. However, further experiments are needed to confirm the functional pathways and hub genes associated with AMI.