Identification of Ferroptosis-Related Hub Genes and Their Association with Immune Infiltration in Chronic Obstructive Pulmonary Disease by Bioinformatics Analysis.

Purpose: Ferroptosis and immune infiltration are involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). We aim to identify ferroptosis-related hub genes and analyze their association with immune infiltration in COPD through bioinformatics methods.

Materials And Methods: The mRNA microarray data of GSE38974 were downloaded from Gene Expression Omnibus to obtain differentially expressed genes (DEGs). The DEGs were intersected with ferroptosis-related genes (FRGs) from FerrDb to obtain differentially expressed FRGs. GO and KEGG enrichment and protein-protein interaction (PPI) analyses of differentially expressed FRGs were conducted in R software and STRING database. The key module and hub genes were screened by Cytoscape software. MiRNAs, transcription factors and signal molecules were predicted in miRNet and NetworkAnalyst. The disease correlation in the Comparative Toxicomics Database (CTD) and the receiver operating characteristic (ROC) curves of hub genes were analyzed. Immune infiltration was evaluated by CIBERSORT algorithm. Spearman correlation analyses were conducted between hub genes and differentially infiltrated immune cells.

Results: Fifteen differentially expressed FRGs were identified, which were enriched in some terms involving airway inflammatory responses and structural remodeling. Five hub genes were selected including HIF1A, IL6, PTGS2, CDKN1A and ATM. Inference scores in CTD indicated their association with COPD. Two miRNAs, five transcription factors and one signal molecule were predicted. The combination of hub genes could be a fine diagnostic indicator of COPD (AUC: 0.981, CI: 0.940-1.000). Immune infiltration evaluation showed that monocytes and M0 macrophages were upregulated in COPD lung tissues, while CD8 T cells, activated NK cells, M2 macrophages, resting dendritic cells and resting mast cells were downregulated. The hub genes were significantly associated with differentially infiltrated immune cells.

Conclusion: We identified five ferroptosis-related hub genes (HIF1A, IL6, PTGS2, CDKN1A and ATM) in COPD, and found that they may influence the pathogenesis of COPD by regulating ferroptosis and thus affecting infiltrating immune cells.