Screening of Lipid Metabolism-Related Genes as Diagnostic Indicators in Chronic Obstructive Pulmonary Disease.

Objective: It has been observed that local and systemic disorders of lipid metabolism occur during the development of chronic obstructive pulmonary disease (COPD), but no specific mechanism has yet been identified.

Methods: The mRNA microarray dataset GSE76925 of COPD patients was downloaded from the Gene Expression Omnibus database and screened for differentially expressed genes (DEGs). Lipid metabolism-related genes (LMRGs) were extracted from the Kyoto Encyclopedia of Genes and Genomes database and Molecular Signature Database. The DEGs were intersected with LMRGs to obtain differentially expressed lipid metabolism-related genes (DeLMRGs). GO enrichment analysis and KEGG pathway analysis were performed on DeLMRGs, and protein-protein interaction networks were constructed and screened to identify hub genes. The GSE8581 validation set and further ELISA experiments were used to validate key DeLMRG expression.

Results: Differential analysis of dataset GSE76925 identified 587 DEGs, of which 62 genes were up-regulated and 525 were down-regulated. Taking the intersection of 587 DEGs with 1102 LMRGs, 20 DeLMRGs were obtained, including 1 up-regulated gene and 19 down-regulated genes. 10 hub genes were screened by cytohubba plugin, including 9 down-regulated genes and , as well as the only up-regulated gene . Validation of the identified 10 DeLMRGs using the validation set GSE8581 revealed that and expression levels differed between the two groups. We further constructed the ceRNA network of and . Cell experiments also showed that expression was up-regulated and expression was down-regulated in CSE-treated RAW264.7 and THP-1 cells.

Conclusion: Based on a comprehensive bioinformatic analysis of lipid metabolism genes, we identified and as potentially significant biomarkers of COPD. These biomarkers may represent promising targets for COPD diagnosis and treatment.