Identification and Analysis of Necroptosis-Related Genes in COPD by Bioinformatics and Experimental Verification

Abstract

Chronic obstructive pulmonary disease (COPD) is a heterogeneous and complex progressive inflammatory disease. Necroptosis is a newly identified type of programmed cell death. However, the role of necroptosis in COPD is unclear. This study aimed to identify necroptosis-related genes in COPD and explore the roles of necroptosis and immune infiltration through bioinformatics. The analysis identified 49 differentially expressed necroptosis-related genes that were primarily engaged in inflammatory immune response pathways. The infiltration of CD8+ T cells and M2 macrophages in COPD lung tissue was relatively reduced, whereas that of M0 macrophages was increased. We identified 10 necroptosis-related hub genes significantly associated with infiltrated immune cells. Furthermore, 7 hub genes, CASP8, IL1B, RIPK1, MLKL, XIAP, TNFRSF1A, and CFLAR, were validated using an external dataset and experimental mice. CFLAR was considered to have the best COPD-diagnosing capability. TF and miRNA interactions with common hub genes were identified. Several related potentially therapeutic molecules for COPD were also identified. The present findings suggest that necroptosis occurs in COPD pathogenesis and is correlated with immune cell infiltration, which indicates that necroptosis may participate in the development of COPD by interacting with the immune response.