Ferroptosis-related genes MDM2 and CDKN1A as reliable biomarkers for COPD

Abstract Objective Chronic obstructive pulmonary disease (COPD) is characterized by inflammation and immune response. However, the relationship of 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 with WGCNA, GO, and KEGG enrichment, PPI network, LASSO-COX, and ROC curves 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 H&E and Masson stainning, and Western blot analysis in the CS and LPS-induced COPD mice. Results MDM2 and CDKN1A were identified as the hub genes in all COPD patients and their expressions were significantly upregulated in lung tissues of COPD mice. 17 types of respiratory tract diseases were markedly associated with MDM2 and CDKN1A. The 2 genes markedly correlated to 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 neutrophils-involved inflammation. One drug with potential clinical application value was identified.