Identification of Key Pathways and Genes of Acute Respiratory Distress Syndrome Specific Neutrophil Phenotype

Abstract

Despite over 50 years of clinical and basic studies, acute respiratory distress syndrome (ARDS) is still a critical challenge with high mortality worldwide. The severity of neutrophil activation was associated with disease severity. However, the detailed pathophysiology of the circulating polymorphonuclear neutrophil activation in ARDS remains unclear. To identify key pathways and genes in the ARDS-specific neutrophil phenotype distinct from sepsis, the datasets of blood polymorphonuclear neutrophils (PMNs) from patients with ARDS (GSE76293) and from sepsis patients (GSE49757) were chosen from the Gene Expression Omnibus (GEO) and analyzed using bioinformatics methods. A total of 220 differential expressed genes (DEGs) were overlapped between GSE49757 and GSE76293 in a Venn diagram. Pathway enrichment analysis results showed that DEGs in GSE76293 were mainly enriched in the MAPK signaling pathway, FoxO signaling pathway, and AMPK signaling pathway relative to GSE49757. We identified 30 hub genes in the protein-protein interaction network. By comparing with GSE49757, we speculated that GAPDH, MAPK8, PIK3CB, and MMP9 may play important roles in the progression of ARDS-specific circulating neutrophil activation. The findings may provide novel insights into the development of promising targets for the diagnosis and treatment of ARDS in the future.