Pediatr Allergy Immunol Pulmonol. 2025 Nov 17. doi: 10.1177/2151321X251395599. Online ahead of print.
ABSTRACT
Background: Bronchopulmonary dysplasia (BPD), a common pulmonary condition in infants causing neonatal death, has a complicated pathogenic mechanism. As the new iron-dependent cell death type, ferroptosis can result from lipid peroxidation and exert a critical effect on the pathogenic mechanism of BPD. This study aimed to investigate ferroptosis-related genes with regard to their expression patterns and functional roles in BPD. Methods: Clinical and gene expression data were obtained based on the Gene Expression Omnibus (GEO) database, and the web-based analysis approach GEO2R was used for selecting differentially expressed genes (DEGs). For significant ferroptosis-related DEGs (FDEGs), their bioinformatic functions and molecular interactions were explored using the WEB-based Gene Set Analysis Toolkit (WebGestalt) and Metascape, protein-protein interaction network analysis, and Kyoto Encyclopedia of Genes and Genomes enrichment. In addition, hub FDEG expression levels in BPD were verified through quantitative reverse transcription polymerase chain reaction (RT-qPCR). Results: There were totally 3,673 DEGs detected in BPD infants compared with controls, including 36 FDEGs with upregulation, whereas 13 with downregulation. Functional enrichment analysis revealed the significant activation of biological processes in response to stress and ferroptosis. Through RT-qPCR validation, five hub FDEGs were identified, including mitogen-activated protein kinase 14 (MAPK14), tumor antigen p53 (TP53), signal transducer and activator of transcription 3 (STAT3), toll-like receptor 4 (TLR4), and dual-specificity protein phosphatase 1 (DUSP1). Based on the outcomes of receiver operating characteristic curve analysis, the area under the curve values of these genes were >0.7, revealing that they might be used to identify BPD. Conclusions: The results in this study shed more insights on the diagnosis and mechanism of ferroptosis in BPD. Further research should be carried out to assess its clinical utility.
PMID:41248932 | DOI:10.1177/2151321X251395599
