Bioinformatics analysis of immune infiltration and cell cycle hub genes in atopic dermatitis

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports Pub Date : 2025-09-08 DOI:10.1016/j.bbrep.2025.102253

Xiaoyun Liu , Xizi Lu , Li Wang , Qian Du , Xiang Li , Yi Li , Xiaofeng Ding , Yongxian Lai , Xiaogang Chen

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引用次数: 0

Abstract

Background

Atopic dermatitis (AD) is a chronic inflammatory skin disease with complex pathogenesis. This study integrated bioinformatics and experimental validation to elucidate the molecular pathways and discover novel therapeutic targets for AD diagnostic and treatment.

Methods

Transcriptomic datasets GSE182740 (training cohort, n = 75) and GSE5667 (validation cohort, n = 34) were analyzed. DEGs identified via GEO2R (|logFC|>2, p < 0.01) underwent KEGG/GO enrichment (Metascape; min overlap = 3, p < 0.01). STRING-constructed PPI networks (interaction score>0.4) visualized in Cytoscape (v3.10.1) revealed top 5 hub genes by CytoHubba MCC scoring. Immune cell infiltration patterns were quantified using ssGSEA software, with in vitro validation conducted in TNF-α/IFN-γ-stimulated keratinocytes.

Results

Among 979 significant DEGs, inflammation-related pathways (IL-17, TNF-α, PI3K-Akt, p < 0.05) were enriched. PPI analysis revealed five cell cycle-regulating hub genes (AURKA, BUB1B, CCNB1, MELK, and TTK), all upregulated in AD lesions. In vitro experiments confirmed the upregulation of these hub genes in AD. These genes correlated significantly with activated CD4 T cells, Th2 cells, Treg cells, and central memory CD8 T cells (p < 0.05). In vitro experiments confirmed the overexpression of five hub genes in keratinocytes induced by inflammatory factors.

Conclusion

This study identified five hub genes driving AD by disrupting keratinocytes cell cycle regulation. These genes mediated keratinocytes-immune interactions, providing novel targets for AD therapy.

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特应性皮炎免疫浸润和细胞周期中心基因的生物信息学分析

背景：过敏性皮炎（AD）是一种慢性炎症性皮肤病，发病机制复杂。本研究将生物信息学与实验验证相结合，阐明AD的分子通路，发现新的治疗靶点。方法分析转录组学数据集GSE182740（训练组，n = 75）和GSE5667（验证组，n = 34）。通过GEO2R鉴定的DEGs （|logFC|>2, p < 0.01）进行了KEGG/GO富集（Metascape; min overlap = 3, p < 0.01）。在Cytoscape （v3.10.1）中可视化的字符串构建的PPI网络（相互作用评分>；0.4）显示了CytoHubba MCC评分前5位的枢纽基因。使用ssGSEA软件定量免疫细胞浸润模式，并在TNF-α/IFN-γ刺激的角质形成细胞中进行体外验证。结果979个显著deg中，炎症相关通路（IL-17、TNF-α、PI3K-Akt, p < 0.05）均富集。PPI分析显示，5个细胞周期调节中心基因（AURKA、BUB1B、CCNB1、MELK和TTK）在AD病变中均上调。体外实验证实了这些中枢基因在AD中的上调。这些基因与活化的CD4 T细胞、Th2细胞、Treg细胞和中央记忆CD8 T细胞显著相关（p < 0.05）。体外实验证实炎症因子诱导的角质形成细胞中有5个hub基因过表达。结论本研究通过破坏角质形成细胞的细胞周期调节，确定了5个中枢基因驱动AD。这些基因介导角化细胞-免疫相互作用，为阿尔茨海默病治疗提供了新的靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biochemistry and Biophysics Reports Biochemistry, Genetics and Molecular Biology-Biophysics

CiteScore

4.60

自引率

0.00%

发文量

191

审稿时长

59 days

期刊介绍： Open access, online only, peer-reviewed international journal in the Life Sciences, established in 2014 Biochemistry and Biophysics Reports (BB Reports) publishes original research in all aspects of Biochemistry, Biophysics and related areas like Molecular and Cell Biology. BB Reports welcomes solid though more preliminary, descriptive and small scale results if they have the potential to stimulate and/or contribute to future research, leading to new insights or hypothesis. Primary criteria for acceptance is that the work is original, scientifically and technically sound and provides valuable knowledge to life sciences research. We strongly believe all results deserve to be published and documented for the advancement of science. BB Reports specifically appreciates receiving reports on: Negative results, Replication studies, Reanalysis of previous datasets.