Identification of biomarkers associated with mitochondrial dysfunction and programmed cell death in chronic...

Research has demonstrated that the homeostasis of mitochondria and programmed cell death (PCD) are intimately linked to chronic obstructive pulmonary disease (COPD). Consequently, identifying biomarkers of COPD from mitochondria-related genes (MRGs) and programmed cell death-related genes (PCD-RGs) is of paramount importance.

Differentially expressed genes (DEGs) from the GSE42057 dataset and COPD-related genes (COPD-RGs) via weighted gene co-expression network analysis (WGCNA) were intersected with MRGs and PCD-RGs to select candidates. Machine learning identified biomarkers, validated across GSE42057 and GSE94916 datasets. Pathway enrichment, immune infiltration, and drug prediction analyses were performed.

Eight candidate genes were derived from intersecting DEGs, COPD-RGs, MRGs, and PCD-RGs. Five biomarkers (BCL2, CCR7, FAM162A, FOXO1, RPS3) were identified, showing consistent dysregulation in COPD. These biomarkers activated the "ribosome" pathway. CCR7 and FOXO1 correlated positively with naïve B cells, while BCL2 negatively correlated with M0 macrophages. BCL2 exhibited strong binding to dolastatin 10, beauvericin, and micellar paclitaxel. RT-qPCR confirmed biomarker expression.

BCL2, CCR7, FAM162A, FOXO1, and RPS3 are biomarkers for COPD, providing a new breakthrough point for the treatment of this disease.