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ORIGINAL RESEARCH article

Front. Med.

Sec. Dermatology

Volume 12 - 2025 | doi: 10.3389/fmed.2025.1615865

Exploring the Role of Ferroptosis in Pemphigus: Identification of Diagnostic Markers and Regulatory Mechanisms

Provisionally accepted
Jing  MaoJing Mao1Jianping  LanJianping Lan2Zheyu  ZhuangZheyu Zhuang1Ying  ChenYing Chen1Yushan  OuYushan Ou1Xinhong  SuXinhong Su1Xueting  ZengXueting Zeng1Fuchen  HuangFuchen Huang1Zequn  TongZequn Tong1Xiaoqing  LvXiaoqing Lv1Hui  KeHui Ke1Zhenlan  WuZhenlan Wu1Ying  ZouYing Zou1Bo  ChengBo Cheng1Chao  JiChao Ji1*Ting  GongTing Gong3
  • 1Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, People's Republic of China., Fuzhou, China
  • 2Mindong Hospital, Fujian Medical University, Ningde, Fujian, China
  • 3Department of Dermatology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China

The final, formatted version of the article will be published soon.

Background: Pemphigus is an autoimmune blistering disorder characterized by the loss of cell adhesion in the epidermis. Recent studies have suggested a potential link between ferroptosis, a form of regulated cell death dependent on iron, and various diseases. However, the role of ferroptosis-related genes in pemphigus remains largely unexplored. This study aims to investigate the expression patterns and potential biological functions of ferroptosis-related genes in pemphigus, as well as their regulatory mechanisms.Methods: To achieve this, skin samples from five pemphigus patients and five healthy controls were collected from Fujian Medical University Union Hospital. Additionally, we processed the GSE53873 microarray dataset, which includes 19 pemphigus samples and 5 controls. Differentially expressed genes (DEGs) were identified using the limma R package, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to identify co-expressed gene modules related to pemphigus. Machine learning algorithms such as Least Absolute Shrinkage and Selection Operator (LASSO), Random Forest (RF), and eXtreme Gradient Boosting (XGBoost) were used to select key ferroptosis-related genes. Immune cell infiltration was assessed using CIBERSORT and single-sample Gene Set Enrichment Analysis (ssGSEA). Finally, experimental validation was conducted through real-time quantitative PCR, transmission electron microscopy, and drug prediction.Results: Our results identified 1,840 DEGs in pemphigus patients compared to controls, with significant enrichment in pathways such as PI3K-Akt signaling and fatty acid metabolism. Eleven co-expression modules were identified via WGCNA, with the module highlighted in lightcyan colour showing the strongest correlation with pemphigus. Machine learning highlighted ACSL4, SAT2, and XBP1 as potential hub genes with high diagnostic value. Immune analysis revealed increased proportions of activated CD8+ T cells and natural killer cells in pemphigus patients. Experimental validation confirmed the presence of ferroptosis morphological features in patient samples.Conclusions: In conclusion, this study elucidates the involvement of ferroptosis-related genes in pemphigus pathogenesis and identifies potential biomarkers for diagnosis. Further research is warranted to explore therapeutic strategies targeting these pathways.

Keywords: Pemphigus, WGCNA, ferroptosis, Immune infiltration, biomarker

Received: 22 Apr 2025; Accepted: 03 Jun 2025.

Copyright: © 2025 Mao, Lan, Zhuang, Chen, Ou, Su, Zeng, Huang, Tong, Lv, Ke, Wu, Zou, Cheng, Ji and Gong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Chao Ji, Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, People's Republic of China., Fuzhou, China

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