Objective To investigate the expression of glycolysis-related genes in the pathogenesis of chronic obstructive pulmonary disease (COPD) utilizing bioinformatics methods and the potential role of these genes in mediating immune dysregulation in COPD through their influence on the glycolysis-controlled lactylation pathway.

Methods The COPD-related dataset GSE20257 was sourced from the GEO database, followed by differential gene correlation analysis and weighted gene co-expression network analysis (WGCNA). The relevant genes identified from both datasets were intersected with the glycolysis gene set to filter for common differentially expressed genes, which were subsequently subjected to enrichment analysis. Subsequently, key genes involved in glycolysis were identified using the LASSO and SVM-RFE algorithms. After subtyping, GSEA analysis was conducted. An immune infiltration analysis was performed to evaluate the extent of immune cell infiltration in COPD samples and explore the correlation between key genes and immune cells. Finally, the relative expression levels of glycolytic key genes in human and mouse lung tissues were assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR).

Results After screening 16 commonly differentially expressed genes through WGCNA analysis and dataset intersection, ME1 and ALDH3A1 were ultimately identified as key genes using LASSO and SVM-RFE algorithms. Cluster analysis classified the samples into two subtypes, and GSEA analysis of the differentially expressed genes between these subtypes revealed significant enrichment in the cell cycle, chemokine signaling pathway, JAK-STAT signaling pathway, among others. Compared with the control group, the gene expression levels of ME1 and ALDH3A1 in the lung tissue of the COPD group were significantly increased (P < 0.05). Additionally, the gene expression levels of ME1 and ALDH3A1 in the lung tissue of mice in the chronic tobacco smoke exposure (CS) group were also significantly increased compared with those in the air group (P < 0.01).

Conclusion The glycolysis-related genes ME1 and ALDH3A1 may mediate immune dysregulation in COPD by regulating the lactate pathway through glycolysis.