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基于综合生物信息学分析鉴定小儿和成人溃疡性结肠炎的枢纽基因、关键通路和免疫细胞浸润特征。

Identifying Hub Genes, Key Pathways and Immune Cell Infiltration Characteristics in Pediatric and Adult Ulcerative Colitis by Integrated Bioinformatic Analysis.

机构信息

Medical School of Nanchang University, 603 Bayi Road, Nanchang, 330006, Jiangxi, China.

出版信息

Dig Dis Sci. 2021 Sep;66(9):3002-3014. doi: 10.1007/s10620-020-06611-w. Epub 2020 Sep 25.

Abstract

BACKGROUND AND AIMS

In the present study, we investigated the differentially expressed genes (DEGs), pathways and immune cell infiltration characteristics of pediatric and adult ulcerative colitis (UC).

METHODS

We conducted DEG analysis using the microarray dataset GSE87473 containing 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.

RESULTS

In 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.

CONCLUSIONS

Our 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.

摘要

背景与目的

本研究旨在探讨儿童和成人溃疡性结肠炎(UC)的差异表达基因(DEGs)、通路和免疫细胞浸润特征。

方法

我们从基因表达综合数据库中下载了包含 19 例儿童和 87 例成人 UC 样本的微阵列数据集 GSE87473,进行 DEG 分析。使用 Metascape 进行基因本体论和通路富集分析。我们构建了 DEGs 的蛋白质-蛋白质相互作用(PPI)网络和药物-靶点相互作用网络,使用 Cytoscape 识别枢纽模块和基因,并使用 CIBERSORT 分析儿童和成人 UC 中的免疫细胞浸润。

结果

从数据集中筛选出 1700 个 DEGs。这些基因主要富集在细胞间项目中,与细胞连接、细胞黏附、肌动蛋白细胞骨架和跨膜受体信号通路有关,以及细胞内项目中,与 RNA 的剪接、代谢和定位有关。CDC42、POLR2A、RAC1、PIK3R1、MAPK1 和 SRC 被确定为枢纽 DEGs。免疫细胞浸润分析显示,儿童 UC 中幼稚 B 细胞、静息记忆 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,而记忆 B 细胞、滤泡辅助 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。

结论

本研究表明,CDC42、POLR2A、RAC1、PIK3R1、MAPK1 和 SRC 等枢纽基因以及包括 B 细胞、T 细胞、单核细胞、巨噬细胞和肥大细胞在内的免疫细胞在儿童和成人 UC 的病理差异中发挥重要作用,可能作为 UC 诊断和治疗的潜在生物标志物。

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