Identification of oxidative stress-related hub genes and immune infiltration characterization in chronic spontaneous urticaria.

Authors

Juan Li, Hongwan Gan, Yu Zhong, Hongfu Liu

Published in

Molecular genetics and genomics : MGG. Volume 301. Issue 1. May 15, 2026. Epub May 15, 2026.

Abstract

Chronic spontaneous urticaria (CSU) is an inflammatory skin disorder that substantially impairs patients' quality of life, yet its underlying pathogenesis remains incompletely understood. Oxidative stress (OS) has been proposed as a key contributing factor; however, the molecular mechanisms involved and their link to immune dysregulation are still unclear. This study aimed to systematically identify OS-related hub genes in CSU, investigate their association with immune infiltration, and evaluate their diagnostic potential. Expression profiles for urticaria were retrieved from the Gene Expression Omnibus (GEO) database. WGCNA identified OS-related module genes. Differential analysis, GSEA, PPI network, and ROC curve were used to screen OS-related hub genes, with their associations with immune infiltration and potential drug targets analyzed. Additionally, clinical blood samples from patients with CSU were collected to validate the expression levels of the hub genes via quantitative real-time PCR (qRT-PCR). Ten OS-related hub genes (e.g., HMGB1, PSMD1) were screened, with ROC AUC values > 0.76, indicating high diagnostic validity. Immune infiltration analysis revealed pronounced infiltration of 22 immune cell types in CSU patients, while hub gene HMGB1 showed significant negative correlations with activated dendritic cells and γδ T-cell abundance. 33 potential drugs targeting OS-related hub genes were predicted using DGIdb database. The qRT-PCR verification showed that the expression trends of the 9 candidate genes (HIST1H4H, HIST1H4D, SMARCC2, HMGB1, DDB2, TCF7L2, ITGA8, IRF4, and HSPA4) in the clinical samples were consistent with the results of the bioinformatics analysis, all exhibiting high diagnostic value (AUC > 0.76, p < 0.05). In this study, ten OS-related hub genes were identified, nine of which were validated for their diagnostic value in clinical samples. Several potential drug targets were also predicted. These findings provide new insights into the molecular classification, early diagnosis, and targeted therapy of CSU. Future studies involving larger clinical cohorts are warranted to validate these targets and further elucidate their roles in OS-driven CSU pathogenesis, thereby facilitating clinical translation.

PMID:
42138757
Bibliographic data and abstract were imported from PubMed on 14 Jun 2026.

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