Abstract
Chronic obstructive pulmonary disease (COPD) is a common respiratory issue caused by smoking and pollution, resulting in airway obstruction. The aim of this study was to investigate a prognostic model for genes related to apoptosis and mitophagy in COPD. This study investigates the molecular mechanisms linking COPD with PANoptosis and mitophagy, 2 critical cellular processes. Firstly, we integrated Gene Expression Omnibus datasets (GSE10006 and GSE20257) to analyze the differential expression of genes associated with PANoptosis and mitophagy in COPD. Batch effects were removed using the R package sva, followed by differential expression analysis using limma. Next, gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed for PANoptosis and mitochondrial autophagy related genes (PAMRDEGs). Then, STRING and GeneMANIA were used to construct protein-protein interaction network of PAMRDEGs, and ChIPBase and StarBase were used to create regulatory network. Finally, The expression of key genes was verified, the diagnostic efficacy was evaluated by receiver operating characteristic curve analysis, and the immune characteristics related to COPD were explored by immune infiltration analysis. A total of 7 PAMRDEGs were obtained, namely AIM2, DNM1L, MAPK1, CASP8, CDK1, SAMHD1, NLRP3, which showed significant expression changes in COPD, linked to inflammatory response pathways like NOD-like receptor and tumor necrosis factor signaling pathway. Immune infiltration analysis revealed a notable negative correlation with M2 macrophages, highlighting the immune microenvironments importance in COPD progression. This study highlights the critical roles of PANoptosis and mitophagy-related genes in the pathogenesis of COPD, suggesting potential therapeutic targets. In the future, in-depth functional experiments and prospective large sample cohort validation are needed to further clarify the regulatory mechanism of the key targets and promote their clinical translation and application.