Abstract
OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is characterized by inflammation and an immune response. However, the relationship between ferroptosis and COPD remains unknown. We aim to identify pivotal ferroptosis-related biomarkers in COPD and explore their roles in immune infiltration landscapes. METHODS: Differentially expressed genes (DEGs) were obtained from all current datasets of peripheral blood and lung tissues associated with COPD. DEGs were intersected with ferroptosis-related genes (FRGs) from FerrDb database to obtain FRDEGs. Hub FRDEGs were evaluated using WGCNA, GO, and KEGG enrichment, PPI network analysis, LASSO-COX, and ROC curve analysis, and validated in blood of COPD patients. The association between hub FRDEGs and COPD was investigated. The role of hub FRDEGs in 17 types of respiratory tract diseases was analyzed, and potential drugs targeting these FRDEGs were predicted via CMAP drug database. Importantly, MDM2 and CDKN1A expressions were identified and verified by H&E and Masson staining, and Western blot analysis in the CS and LPS-induced COPD mice. RESULTS: MDM2 and CDKN1A were identified as hub genes in all COPD patients, and their expressions were significantly upregulated in the lung tissues of COPD mice. 17 types of respiratory tract diseases were markedly associated with MDM2 and CDKN1A. The 2 genes were correlated with neutrophils. MDM inhibitor (AMG-232) was screened as a potentially key drug affecting MDM2. CONCLUSION: MDM2 and CDKN1A could be potential targets for COPD by regulating neutrophil-involving inflammation. One drug with potential clinical application value was identified.