Identification and Validation of Autophagy-Related Genes in Chronic Obstructive Pulmonary Disease

Purpose: Autophagy plays essential roles in the development of COPD.We aim to identify and validate the potential autophagy-related genes of COPD through bioinformatics analysis and experiment validation.Methods: The mRNA expression profile dataset GSE38974 was obtained from GEO database.The potential differentially expressed autophagy-related genes of COPD were screened by R software.Then, protein-protein interactions (PPI), correlation analysis, gene-ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied for the differentially expressed autophagy-related genes.Finally, RNA expression of top five differentially expressed autophagy-related genes was validated in blood samples from COPD patients and healthy controls by qRT-PCR.Results: A total of 40 differentially expressed autophagy-related genes (14 up-regulated genes and 26 down-regulated genes) were identified between 23 COPD patients and 9 healthy controls.The PPI results demonstrated that these autophagy-related genes interacted with each other.The GO and KEGG enrichment analysis of differentially expressed autophagy-related genes indicated several enriched terms related to autophagy and mitophagy.The results of qRT-PCR showed that the expression levels of HIF1A, CDKN1A, BAG3, ERBB2 and ATG16L1 in COPD patients and healthy controls were consistent with the bioinformatics analysis results from mRNA microarray. Conclusion:We identified 40 potential autophagy-related genes of COPD through bioinformatics analysis.HIF1A, CDKN1A, BAG3, ERBB2 and ATG16L1 may affect the development of COPD by regulating autophagy.These results may expand our understanding of COPD and might be useful in the treatment of COPD.