Neutrophil Infiltration Characterized by Upregulation of S100A8, S100A9, S100A12 and CXCR2 Is Associated With the Co-Occurrence of Crohn's Disease and Peripheral Artery Disease.
Neutrophil Infiltration Characterized by Upregulation of S100A8, S100A9, S100A12 and CXCR2 Is Associated With the Co-Occurrence of Crohn's Disease and Peripheral Artery Disease.
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DOI：
10.3389/fimmu.2022.896645
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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克罗恩病（CD）和外周动脉疾病（PAD）密切相关。CD和PAD共存的病理生理机制尚不清楚。本研究的目的是通过对公共RNA测序数据库的定量生物信息学分析来研究介导CD和PAD共同发生的关键分子和途径。CD（GSE 111889）和PAD（GSE 120642）的数据集从基因表达综合数据库（GEO）下载。差异表达基因（DEG）分析使用的'edgeR'和'limma'软件包R。通过基因本体论和京都百科全书对常见DEG进行分析，探讨DEG的功能。蛋白质-蛋白质相互作用（PPI）网络建立的检索工具相互作用基因（STRING）数据库和可视化的Cytoscape。使用插件cytoHubba选择Hub基因。在GSE 95095（CD）和GSE 134431（PAD）中进行Hub基因验证。采用受试者工作特征曲线评价枢纽基因的预测价值。进行基因集富集分析和枢纽基因的免疫浸润。共鉴定了54种常见的DEG（2种下调，52种上调）。中性粒细胞趋化性、中性粒细胞迁移、细胞因子和细胞因子受体途径在CD和PAD中富集。验证后，S100 A8、S100 A9、S100 A12和CXCR 2被鉴定为枢纽基因，CD和PAD的曲线下面积均> 0.7。神经元浸润与中枢基因的上调相关。CD和PAD中S100 A8、S100 A9、S100 A12和CXCR 2的高表达与中性粒细胞活化、中性粒细胞趋化、中性粒细胞迁移等免疫过程密切相关。这项生物信息学研究阐明了S100 A8、S100 A9、S100 A12和CXCR 2作为克罗恩病和外周动脉疾病共同发生的枢纽基因。中性粒细胞浸润调节的炎症和免疫调节在CD和PAD的发生发展中起核心作用，可能是诊断和治疗的潜在靶点。
Crohn’s disease (CD) and peripheral arterial disease (PAD) are closely related. The pathophysiological mechanisms underlying the coexistence of CD and PAD are unknown. The aim of this study was to investigate the key molecules and pathways mediating the co-occurrence of CD and PAD through quantitative bioinformatic analysis of a public RNA sequencing database. Datasets of CD (GSE111889) and PAD (GSE120642) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were analyzed using the ‘edgeR’ and ‘limma’ packages of R. Gene Ontology and Kyoto Encyclopedia analyses of common DEGs were performed to explore the functions of DEGs. Protein–protein interaction (PPI) networks were established by the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized by Cytoscape. Hub genes were selected using the plugin cytoHubba. Hub gene validation was performed in GSE95095 for CD and GSE134431 for PAD. Receiver operating characteristic curves were used to evaluate the predictive values of the hub genes. Gene set enrichment analysis and immune infiltration of the hub genes were performed. A total of 54 common DEGs (2 downregulated and 52 upregulated) were identified. Pathways of neutrophil chemotaxis, neutrophil migration and cytokine and cytokine receptors were enriched in CD and PAD. S100A8, S100A9, S100A12 and CXCR2 were identified as hub genes after validation, with all area under the curve > 0.7 for both CD and PAD. Neutrophil infiltration was associated with upregulation of the hub genes. Pathways of immune processes, including neutrophil activation, neutrophil chemotaxis, neutrophil migration were significantly correlated with high expression of S100A8, S100A9, S100A12 and CXCR2 in both CD and PAD. This bioinformatic study elucidates S100A8, S100A9, S100A12 and CXCR2 as hub genes for the co-occurrence of Crohn’s disease and peripheral artery disease. Inflammation and immune regulation modulated by neutrophil infiltration play a central role in the development of CD and PAD and may be potential targets for diagnosis and treatment.
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作者：
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