Abstract / Summary
Abstract Background Studies have suggested that lipotoxicity may play a significant role in the etiology of chronic obstructive pulmonary disease (COPD). However, the precise involvement of lipotoxicity-related genes (LRGs) in COPD remains unclear. This study aimed to identify and validate biomarkers associated with LRGs in COPD, potentially paving the way for the development of targeted therapeutic strategies. Methods In the study, COPD-related datasets were sourced from a public database. Biomarkers were ascertained through differential expression analysis, machine learning, and gene expression analyses. A nomogram was developed and evaluated based on these biomarkers. To further explore the underlying biological mechanisms of COPD, functional enrichment analysis, immune infiltration analysis, drug prediction, single-cell RNA sequencing (scRNA-seq), and reverse transcription quantitative PCR (RT-qPCR) analyses were conducted. Results APRT and S100A8 were ascertained as biomarkers for COPD. Notably, APRT exhibited notably lower expression in COPD samples, while S100A8 showed notably higher expression. RT-qPCR analysis further supported these findings. A nomogram was then developed and validated, with the calibration curve indicating its effective ability to predict COPD risk (P = 0.395 in the Hosmer-Lemeshow test). Both biomarkers were found to be significantly co-enriched in the "focal adhesion" pathway. Additionally, 3 immune cell types with notably differential infiltration were identified, and both APRT and S100A8 showed a significant correlation with neutrophils. Furthermore, 27 drugs (such as alteplase and relaxin) targeting APRT, as well as methotrexate targeting S100A8, were predicted. Finally, scRNA-seq analysis ascertained macrophages as a key cell type in COPD. Dynamic expression patterns of both biomarkers were observed during macrophage differentiation: APRT first increases, then decreases, and increases again, while S100A8 initially rises and then declines. Conclusion This study ascertained APRT and S100A8 as biomarkers associated with lipotoxicity in COPD, providing valuable insights that could aid in the development of targeted therapies.