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利用生物信息学分析鉴定金黄色葡萄球菌感染性心内膜炎相关的关键差异表达基因和通路。

Identification of the pivotal differentially expressed genes and pathways involved in Staphylococcus aureus-induced infective endocarditis by using bioinformatics analysis.

机构信息

Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.

出版信息

Eur Rev Med Pharmacol Sci. 2021 Jan;25(1):487-497. doi: 10.26355/eurrev_202101_24420.

DOI:10.26355/eurrev_202101_24420
PMID:33506940
Abstract

OBJECTIVE

Infective endocarditis (IE), particularly by Staphylococcus aureus, is an uncommon bacteremia-associated infection of the endocardium and cardiac valves. Herein, we evaluated predictive noninvasive biomarkers for IE caused by S. aureus through bioinformatics analysis.

MATERIALS AND METHODS

Staphylococcus aureus-associated and IE-associated differentially expressed genes (DEGs) were identified by bioinformatics analysis of the GSE6269 and GSE29161 Gene Expression Omnibus (GEO) datasets. The DEGs were analyzed with the LIMMA package, and the coregulated genes were chosen as the intersection of DEGs between the two datasets, called common differentially expressed genes (CDEGs). The enrichment study of CDEGs was subsequently performed with the DAVID and KOBAS web resources. Finally, protein-protein interaction (PPI) network, microRNA (miRNA)-transcription factor (TF)-mRNA (messenger RNA) regulatory network, and the network of drug-genes were identified.

RESULTS

From GSE6269 and GSE29161, respectively, a total of 201 and 741 DEGs were obtained. Gene Ontology (GO) analysis showed that CDEGs were primarily involved in innate immune response, extracellular exosome, as well as calcium ion binding, while the pathway analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that CDEGs were significantly enriched in the B-cell receptor, IL-17, and NF-kappa B signaling pathways. The hub genes in the PPI network included HP, S100A12, SPI1, CD14, CCR1, S100A9 and so on. In the miRNA-TF-mRNA regulatory network, SPI1 could target miR-361-5p, miR-155-5p, and miR-339-5p in the progression of IE.

CONCLUSIONS

Several pivotal genes and pathways were identified in the progression of S. aureus-induced IE, which may have the potential for early detection.

摘要

目的

感染性心内膜炎(IE),特别是由金黄色葡萄球菌引起的,是一种少见的菌血症相关的心内膜和心脏瓣膜感染。在此,我们通过生物信息学分析评估了金黄色葡萄球菌引起的 IE 的预测性非侵入性生物标志物。

材料和方法

通过生物信息学分析 GSE6269 和 GSE29161 基因表达综合数据库(GEO)数据集,确定了金黄色葡萄球菌相关和 IE 相关差异表达基因(DEGs)。使用 LIMMA 软件包对 DEGs 进行分析,并选择两个数据集之间的 DEGs 的交集作为共同差异表达基因(CDEGs)。随后,使用 DAVID 和 KOBAS 网络资源对 CDEGs 进行富集研究。最后,构建了蛋白质-蛋白质相互作用(PPI)网络、miRNA-转录因子(TF)-mRNA(信使 RNA)调控网络以及药物-基因网络。

结果

分别从 GSE6269 和 GSE29161 中获得了 201 个和 741 个 DEGs。基因本体论(GO)分析表明,CDEGs 主要参与固有免疫反应、细胞外外泌体以及钙离子结合,而京都基因与基因组百科全书(KEGG)通路分析表明,CDEGs 显著富集于 B 细胞受体、IL-17 和 NF-kappa B 信号通路。PPI 网络中的枢纽基因包括 HP、S100A12、SPI1、CD14、CCR1、S100A9 等。在 miRNA-TF-mRNA 调控网络中,SPI1 可以靶向 IE 进展过程中的 miR-361-5p、miR-155-5p 和 miR-339-5p。

结论

在金黄色葡萄球菌诱导的 IE 进展过程中确定了几个关键基因和通路,它们可能具有早期检测的潜力。

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