Bioinformatics analysis combined with untargeted metabolomics reveals lipid metabolism-related genes and their biological markers in chronic spontaneous urticaria.

IF 2.8 3区生物学 Q2 GENETICS & HEREDITY

Frontiers in Genetics Pub Date : 2025-08-18 eCollection Date: 2025-01-01 DOI:10.3389/fgene.2025.1550205

Zhiming Hu, Qiong Wang, Yuqi Wang, Yao Gao, Jianhua Hao, Rui Li, Hua Zhao, Shuping Guo, Hongzhou Cui

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引用次数: 0

Abstract

Background: Chronic spontaneous urticaria (CSU) is an immune-driven skin condition with a multifaceted and not yet fully understood pathogenesis. Although substantial research has been conducted, viable therapeutic targets are still scarce. Studies indicate that disruptions in lipid metabolism significantly influence the development of immune-related disorders. Nevertheless, the precise relationship between lipid metabolism and CSU remains underexplored, warranting further investigation.

Methods: We obtained the GSE72540 and GSE57178 datasets from the Gene Expression Omnibus (GEO) repository. For the GSE72540 dataset, we identified differentially expressed genes (DEGs) and performed weighted gene co-expression network analysis (WGCNA) on them. The identified DEGs were cross-referenced with lipid metabolism-related genes (LMRGs). To identify hub genes, we constructed a protein-protein interaction (PPI) network. These hub genes were validated using the GSE57178 dataset to identify potential diagnostic markers. Additionally, gene set enrichment analysis (GSEA) and receiver operating characteristic (ROC) curve analysis were employed to evaluate their diagnostic potential. In the CSU mouse model, we further validated the expression levels of these hub genes. Finally, untargeted metabolomics was conducted to detect lipid metabolism-related metabolites in the serum of CSU patients.

Result: Using bioinformatics analysis, three hub genes were identified: SLC2A4, PTGS2, and PLA2G2A. In skin tissues from CSU-like mouse models, the mRNA levels of PTGS2 and PLA2G2A were significantly upregulated compared to the control group. Additionally, untargeted metabolomics revealed 60 distinct lipid metabolites, with a marked increase in arachidonic acid levels observed in the CSU group.

Conclusion: PTGS2 and PLA2G2A are key hub genes for CSU, and arachidonic acid can serve as a potential serum biomarker.

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生物信息学分析结合非靶向代谢组学揭示了慢性自发性荨麻疹的脂质代谢相关基因及其生物学标记。

背景：慢性自发性荨麻疹（CSU）是一种免疫驱动的皮肤病，其发病机制是多方面的，但尚未完全了解。尽管已经进行了大量的研究，但可行的治疗靶点仍然很少。研究表明，脂质代谢的中断显著影响免疫相关疾病的发展。然而，脂质代谢与CSU之间的确切关系仍有待进一步研究。方法：从Gene Expression Omnibus （GEO）数据库中获取GSE72540和GSE57178数据集。对于GSE72540数据集，我们确定了差异表达基因（deg），并对其进行加权基因共表达网络分析（WGCNA）。鉴定的deg与脂质代谢相关基因（LMRGs）交叉对照。为了识别中心基因，我们构建了一个蛋白质-蛋白质相互作用（PPI）网络。使用GSE57178数据集对这些中心基因进行验证，以确定潜在的诊断标记。此外，采用基因集富集分析（GSEA）和受试者工作特征（ROC）曲线分析来评估其诊断潜力。在CSU小鼠模型中，我们进一步验证了这些中枢基因的表达水平。最后，采用非靶向代谢组学方法检测CSU患者血清中脂质代谢相关代谢物。结果：通过生物信息学分析，鉴定出3个枢纽基因：SLC2A4、PTGS2和PLA2G2A。在csu样小鼠模型的皮肤组织中，与对照组相比，PTGS2和PLA2G2A的mRNA水平显著上调。此外，非靶向代谢组学显示60种不同的脂质代谢物，在CSU组中观察到花生四烯酸水平显著增加。结论：PTGS2和PLA2G2A是CSU的关键枢纽基因，花生四烯酸可作为潜在的血清生物标志物。

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

Frontiers in Genetics Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

5.50

自引率

8.10%

发文量

3491

审稿时长

14 weeks

期刊介绍： Frontiers in Genetics publishes rigorously peer-reviewed research on genes and genomes relating to all the domains of life, from humans to plants to livestock and other model organisms. Led by an outstanding Editorial Board of the world’s leading experts, this multidisciplinary, open-access journal is at the forefront of communicating cutting-edge research to researchers, academics, clinicians, policy makers and the public. The study of inheritance and the impact of the genome on various biological processes is well documented. However, the majority of discoveries are still to come. A new era is seeing major developments in the function and variability of the genome, the use of genetic and genomic tools and the analysis of the genetic basis of various biological phenomena.