Investigation of the potential value and mechanisms of copper-related death markers PPOX and TBC1D22B in acute respiratory distress syndrome

Studies showed that cuproptosis could play a crucial role in the development and progression of acute respiratory distress syndrome (ARDS). This study aimed to identify biomarkers associated with cuproptosis-related genes (CRGs) in ARDS and to elucidate their potential biological mechanisms. Two gene expression datasets, GSE32707 and GSE66890, were obtained from the GEO database. Differentially expressed genes (DEGs) were screened via differential expression analysis. WGCNA was applied to identify key module genes, which were intersected with DEGs to obtain differentially expressed cuproptosis-related genes (DE-CRGs). Machine learning algorithms were utilized for biomarker screening, followed by confirmation through ROC curve assessment and expression level validation. A nomogram prediction model was constructed to evaluate clinical diagnostic value. Functional enrichment analysis was performed on these biomarkers to elucidate associated biological pathways and molecular functions. Additionally, immune cell infiltration analysis, therapeutic drug prediction, disease association analysis, and RT-qPCR validation were conducted. After screening, 2 biomarkers were identified, namely PPOX and TBC1D22B. The calibration curves, ROC curves, and decision analysis curve (DCA) were analyzed, resulting in a better prediction of the nomogram model. Functional enrichment analysis indicated that PPOX was enriched for pathways such as olfactory transduction and lysosomes, and TBC1D22B was enriched for pathways such as olfactory transduction and endocytosis. Notably, the olfactory transduction and lysosome were pathways co-enriched for both biomarkers. Spearman correlation analysis showed that PPOX was negatively correlated with CD56 natural killer cells, and TBC1D22B had a significantly negative correlation with activated B cells. In addition, 18 drugs were predicted, with cyclosporine co-targeting PPOX and TBC1D22B. The biomarker-associated disease network maps showed 54 predicted diseases, such as carcinogenesis and homozygous variegate porphyria. Finally, RT-qPCR confirmed that PPOX and TBC1D22B were significantly overexpressed in ARDS. We identified 2 biomarkers (PPOX and TBC1D22B) associated with cuproptosis in ARDS and validated PPOX and TBC1D22B, that might be a better diagnostic ability in ARDS.