AbdElneam Ahmed I, Al-Dhubaibi Mohammed S, Bahaj Saleh S, Mohammed Ghada F, Atef Lina M, Siam Walaa A, Elshemally Amany A E, Rhaim Ali I A Abdel, Aziz Sameh S
Departments of Clinical Biochemistry and Basic Medical Sciences, College of Medicine Shaqra University Dawadmi Saudi Arabia.
Molecular Genetics and Enzymology Department, Human Genetics and Genome Research Institute National Research Center Dokki Egypt.
Health Sci Rep. 2025 Sep 26;8(10):e71283. doi: 10.1002/hsr2.71283. eCollection 2025 Oct.
The pathophysiology of drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is complex and poorly understood. Genetic predispositions play a significant role. We aimed to explore the genetic factors and molecular mechanisms driving DRESS, focusing on gene expression, transcription factors (TFs), microRNAs (miRNAs), and chemical interactions.
We utilized RNA-seq data from the GSE160369 data set in the gene expression omnibus (GEO) database to identify differentially expressed genes (DEGs) related to DRESS. The analysis was conducted using GEO2R for identifying upregulated and downregulated genes. Protein-protein interaction (PPI) networks were constructed using STRING and further analyzed with Cytoscape and CytoHubba. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to identify biological pathways. miRNAs and TFs were predicted using bioinformatics tools like TargetScan, miRDB, and ChEA3, while chemical interactions with key genes were explored using CTDbase.
A total of 336 DEGs were identified, including 239 upregulated and 97 downregulated genes. The PPI network highlighted TNF, IL2, and CD40 as central genes involved in immune-related pathways. Functional enrichment analyses revealed significant pathways related to immune activation, such as leukocyte-mediated immunity. We predicted 15 miRNAs, including hsa-miR-1296-5p, and identified 10 TFs, such as MTF1 and NFKB2, which regulate the expression of key genes. Chemical interaction analysis revealed decitabine and tetradecanoylphorbol acetate as prominent agents modulating gene expression.
miRNAs, TFs, and chemical modulators, which play a key role in the development of DRESS syndrome. Knowledge of the molecular underpinnings of DRESS, imperative for therapeutic targets.
药物超敏反应伴嗜酸性粒细胞增多和全身症状（DRESS）综合征的病理生理学复杂，了解甚少。遗传易感性起着重要作用。我们旨在探索驱动DRESS的遗传因素和分子机制，重点关注基因表达、转录因子（TFs）、微小RNA（miRNAs）和化学相互作用。
我们利用基因表达综合数据库（GEO）中GSE160369数据集的RNA测序数据，识别与DRESS相关的差异表达基因（DEGs）。使用GEO2R进行分析以识别上调和下调基因。利用STRING构建蛋白质-蛋白质相互作用（PPI）网络，并进一步用Cytoscape和CytoHubba进行分析。进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析以识别生物途径。使用TargetScan、miRDB和ChEA3等生物信息学工具预测miRNAs和TFs，同时利用CTDbase探索与关键基因的化学相互作用。
共识别出336个DEGs，包括239个上调基因和97个下调基因。PPI网络突出显示TNF、IL2和CD40是参与免疫相关途径的核心基因。功能富集分析揭示了与免疫激活相关的重要途径，如白细胞介导的免疫。我们预测了15个miRNAs，包括hsa-miR-1296-5p，并识别出10个TFs，如MTF1和NFKB2，它们调节关键基因的表达。化学相互作用分析显示地西他滨和十四酰佛波醇乙酸酯是调节基因表达的重要药物。
miRNAs、TFs和化学调节剂在DRESS综合征的发生发展中起关键作用。了解DRESS的分子基础对治疗靶点至关重要。
