Bioinformatics analyses and experimental validation of ferroptosis-related genes in bronchopulmonary dysplasia pathogenesis

Abstract

AbstractObjectiveWe aimed to study the involvement of ferroptosis in the pathogenesis of bronchopulmonary dysplasia (BPD) by conducting bioinformatics analyses and identifying and validating the associated ferroptosis-related genes to explore new directions for treating BPD.MethodsThe dataset GSE32472 on BPD was downloaded from the public genome database. Using R language, differentially expressed genes (DEGs) between the BPD and normal group were screened. In the present study, we adopted weighted gene correlation network analysis (WGCNA) for identifying BPD-related gene modules and ferroptosis-related genes were extracted from FerrDb. Their results were intersected to obtain the hub genes. After that, to explore the hub gene-related signaling pathways, the hub genes were exposed to gene ontology enrichment analysis. With the purpose of verifying the mRNA expression of the hub genes, a single-gene gene set enrichment analysis and quantitative reverse transcription polymerase chain reaction were conducted. Immune cell infiltration in BPD was analyzed using the CIBERSORT inverse fold product algorithm.ResultsA total of 606 DEGs were screened. WGCNA provided the BPD-related gene module darkgreen4. The intersection of DEGs, intramodular genes, and ferroptosis-related genes revealed six ferroptosis-associated hub genes (ACSL1,GALNT14,WIPI1,MAPK14,PROK2, andCREB5). Receiver operating characteristic curve analysis demonstrated that the hub genes screened for BPD were of good diagnostic significance. According to the results of immune infiltration analysis, the proportions of a cluster of differentiation (CD)8, CD4 naive, and memory resting T cells and M2 macrophage were elevated in the normal group, and the proportions of M0 macrophage, resting mast cell, and neutrophils were increased in the BPD group.ConclusionsA total of six ferroptosis-associated hub genes in BPD were identified in this study, and they may be potential new therapeutic targets for BPD.