Bioinformatics analyses of NET-related hub genes in chronic obstructive pulmonary disease and their association with immune infiltration

Abstract The early diagnosis of chronic obstructive pulmonary disease (COPD), a chronic inflammatory disease, remains challenging. Immune metabolism plays a crucial role in COPD pathogenesis, with neutrophils playing a key role. Although neutrophil extracellular traps (NETs) play a crucial function in preventing infection, irregular and excessive NETs creation can cause COPD to appear and progress. There is still confusion over the precise mechanism, thus more research is required. Herein, we aimed to determine the correlation and diagnostic markers of neutrophil extracellular trap (NET) genes that contribute to immunoinfiltration in COPD. The comprehensive gene expression dataset GSE76925 in the Gene Expression Omnibus database was subjected to differential gene expression analysis. In total, 558 differentially expressed genes were identified, which were then subjected to gene set enrichment analysis. Additionally, the correlation between their expression and immune infiltration was analyzed, and then validated by cluster analysis. Furthermore, 30 differentially expressed NET-related genes were identified and used to construct diagnostic and risk prediction models by random forest and Least absolute shrinkage and selection operator regression analysis. Seven key genes, namely CLEC6A, CTSG, ENTPD4, IRAK4, MAPK1, PIK3CA, and SELPLG, were identified The diagnostic model was validated by generating a receiver operating characteristic curve (ROC) using the GSE38974 dataset. The results revealed that the model exhibited high discrimination ability. Additionally, the models exhibited high diagnostic and risk prediction abilities for COPD. Analysis of single-cell sequencing data from the GSE128033 and GSE163295 datasets revealed that the seven key genes are highly expressed in COPD. Notably, SELPLG and MAPK1 are primarily expressed in monocytes and T cells. Additionally, the genes TLR4, CTSG, IRAK4, SELP, ELPLG, and MAPK1 were revealed to be involved in the pathogenesis of COPD through immune infiltration that leads to NETs. The purpose of this study is to determine the hub genes related to NETs and their association with immune cell infiltration in COPD lung tissue, and provides potential targets for the treatment of COPD.