Contribution of cuproptosis and Cu metabolism-associated genes to chronic obstructive pulmonary disease

Abstract

Airway epithelial cell injury plays a crucial role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, a novel form of Cu-induced programmed cell death known as cuproptosis has not yet been thoroughly investigated in the context of COPD. Clinical reports have suggested that high copper exposure may increase the risk of COPD. In this study, we aimed to determine the expression and potential functions of cuproptosis-related genes and genes associated with copper metabolism in COPD. We initially identified 52 copper metabolism-related genes based on a review of the literature. Subsequently, we calculated the expression levels of these genes using data from four GEO datasets. To gain insights into the activated signalling pathways and underlying mechanisms in COPD patients, we conducted Gene Ontology (GO) and KEGG pathway analyses, examined protein-protein interactions, and performed weighted correlation network analysis. Our findings revealed that 18 key copper metabolism-related genes, including 5 cuproptosis-related genes, were significantly enriched in signalling pathways and biological processes associated with the development of COPD. Further analysis of clinical data and animal experiments confirmed the high expression of certain cuproptosis key regulators, such as DLD and CDKN2A, in both healthy smokers and COPD smokers. Additionally, these regulators exhibited abnormal expression in a COPD rat model. Notably, copper content was found to be elevated in the lung tissues of COPD rats, suggesting its potential involvement in cuproptosis. These findings provide an experimental foundation for further research into the role of cuproptosis in COPD. Targeting copper metabolism-related genes may represent an effective approach for the treatment of COPD.

Keywords: bioinformatics; chronic obstructive pulmonary disease; copper metabolism-related genes; cuproptosis.