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

Abstract

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. 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. 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 PLA2G4A, HPGDS, LEP, PTGES3, LEPR, PLA2G2D, MED21, SPTLC1 and BCHE, as well as the only up-regulated gene PLA2G7. Validation of the identified 10 DeLMRGs using the validation set GSE8581 revealed that BCHE and PLA2G7 expression levels differed between the two groups. We further constructed the ceRNA network of BCHE and PLA2G7. Cell experiments also showed that PLA2G7 expression was up-regulated and BCHE expression was down-regulated in CSE-treated RAW264.7 and THP-1 cells. Based on a comprehensive bioinformatic analysis of lipid metabolism genes, we identified BCHE and PLA2G7 as potentially significant biomarkers of COPD. These biomarkers may represent promising targets for COPD diagnosis and treatment.