Ferroptosis-Related Signature Genes and Immune Landscape in Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Year: 2026
Type: article
Abstract: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is characterized by heightened inflammation and immune dysregulation, yet its underlying molecular mechanisms remain incompletely understood. This study aimed to identify ferroptosis-associated signature genes in AECOPD and to elucidate their immunological implications. METHODS: Differentially expressed ferroptosis-related genes(DEGs) were screened from the GSE112165 dataset (GEO, Gene Expression Omnibus database). Key feature genes were identified using an integrated machine learning and network analysis strategy. External validation was conducted using the GSE22148 dataset, six bronchoalveolar lavage fluid (BALF) samples, and 40 clinical sputum samples. Functional enrichment analysis was performed to delineate relevant biological pathways. Immune and stromal cell infiltration differences were quantified using computational deconvolution frameworks, and their correlations with candidate genes were assessed. RESULTS: Two ferroptosis-related signature genes-SCD(Stearoyl-CoA Desaturase) and FABP4(Fatty Acid Binding Protein 4)-were identified as potential diagnostic markers. Their diagnostic performance was further validated in independent datasets. Among them, FABP4 showed significant downregulation in AECOPD, which was consistently confirmed across BALF and sputum samples. Immune infiltration analysis revealed a strong association between FABP4 expression and neutrophil infiltration. Notably, conventional dendritic cells (cDCs) were significantly reduced in AECOPD patients, suggesting a possible link between ferroptosis and impaired antigen presentation. CONCLUSIONS: (1) This study is the first to comprehensively demonstrate that decreased FABP4 expression may enhance ferroptosis susceptibility by disrupting lipid metabolism, thereby modulating immune cell recruitment and function in AECOPD.(2) The marked reduction of cDCs suggests that ferroptosis may contribute to dysregulated antigen presentation in AECOPD. Taken together, these findings offer novel mechanistic insights into the interplay between ferroptosis and immune dysfunction in AECOPD and provide a theoretical foundation for the development of targeted diagnostic and therapeutic strategies.
Authors: Zhang Yuping, Li Xiangmei, Wang Ruiyang, Zhang Wenbo, Wang Huaqi
Institution: First Affiliated Hospital of Zhengzhou University
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,650
Award: G8741427391
OpenAlex ID: W7129137444