Identifying Hub Genes, Key Pathways and Immune Cell Infiltration Characteristics in Pediatric and Adult Ulcerative Colitis by Integrated Bioinformatic Analysis
Identifying Hub Genes, Key Pathways and Immune Cell Infiltration Characteristics in Pediatric and Adult Ulcerative Colitis by Integrated Bioinformatic Analysis
复制标题
通过综合生物信息学分析识别儿童和成人溃疡性结肠炎的中心基因、关键通路和免疫细胞浸润特征
DOI：
10.1007/s10620-020-06611-w
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发表时间：
2020-09-25
影响因子：
3.1
通讯作者：
Kuang，Bo-hai
中科院分区：
文献类型：
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作者：
Xiu，Meng-xi;Liu，Yuan-meng;Kuang，Bo-hai
背景和目的在本研究中，我们研究了儿童和成人溃疡性结肠炎（UC）的差异表达基因（DEG）、途径和免疫细胞浸润特征。使用Metascape进行基因本体和途径富集分析。我们构建了蛋白质-蛋白质相互作用（PPI）网络和药物-靶点相互作用网络的DEG和确定枢纽模块和基因使用Cytoscape和分析免疫细胞浸润在儿童和成人UC使用CIBERSORT.ResultsIn总，1700 DEG从数据集进行了筛选。这些基因主要富集在与细胞连接、细胞粘附、肌动蛋白细胞骨架和跨膜受体信号通路相关的细胞间项目和与RNA的剪接、代谢和定位相关的细胞内项目中。CDC 42、POLR 2A、RAC 1、PIK 3R 1、MAPK 1和SRC被鉴定为中心DEG。免疫细胞浸润分析显示儿童UC中幼稚B细胞、静息记忆性T辅助细胞、调节性T细胞、单核细胞、M0巨噬细胞和活化肥大细胞的比例较高，沿着记忆性B细胞、滤泡辅助性T细胞、γδ T细胞、M2巨噬细胞和活化树突状细胞的比例较低。MAPK 1和SRC以及免疫细胞（包括B细胞、T细胞、单核细胞、巨噬细胞和肥大细胞）在儿童和成人UC的病理差异中起重要作用，并可作为UC诊断和治疗的潜在生物标志物。
Background and AimsIn the present study, we investigated the differentially expressed genes (DEGs), pathways and immune cell infiltration characteristics of pediatric and adult ulcerative colitis (UC).MethodsWe conducted DEG analysis using the microarray datasetGSE87473containing 19 pediatric and 87 adult UC samples downloaded from the Gene Expression Omnibus. Gene ontology and pathway enrichment analyses were conducted using Metascape. We constructed the protein–protein interaction (PPI) network and the drug–target interaction network of DEGs and identified hub modules and genes using Cytoscape and analyzed immune cell infiltration in pediatric and adult UC using CIBERSORT.ResultsIn total, 1700 DEGs were screened from the dataset. These genes were enriched mainly in inter-cellular items relating to cell junctions, cell adhesion, actin cytoskeleton and transmembrane receptor signaling pathways and intra-cellular items relating to the splicing, metabolism and localization of RNA. CDC42, POLR2A, RAC1, PIK3R1, MAPK1 and SRC were identified as hub DEGs. Immune cell infiltration analysis revealed higher proportions of naive B cells, resting memory T helper cells, regulatory T cells, monocytes, M0 macrophages and activated mast cells in pediatric UC, along with lower proportions of memory B cells, follicular helper T cells, γδ T cells, M2 macrophages, and activated dendritic cells.ConclusionsOur study suggested that hub genes CDC42, POLR2A, RAC1, PIK3R1, MAPK1 and SRC and immune cells including B cells, T cells, monocytes, macrophages and mast cells play vital roles in the pathological differences between pediatric and adult UC and may serve as potential biomarkers in the diagnosis and treatment of UC.