Identification of the key differentially expressed genes and pathways involved in neutrophilia.

Polymorphonuclear neutrophils (PMNs) are the most important determinants in the acute inflammatory response. Pathologically increased numbers of PMNs in the circulation or specific tissues (or both) lead to neutrophilia. However, the genes expressed and pathways involved in neutrophilia have yet to be elucidated. By analysis of three public microarray datasets related to neutrophilia (GSE64457, GSE54644, and GSE94923) and evaluation by gene ontology, pathway enrichment, protein-protein interaction networks, and hub genes analysis using multiple methods (DAVID, PATHER, Reactome, STRING, Reactome FI Plugin, and CytoHubba in Cytoscape), we identified the commonly up-regulated and down-regulated different expressed genes. We also discovered that multiple signaling pathways (IL-mediated, LPS-mediated, TNF-α, TLR cascades, MAPK, and PI3K-Akt) were involved in PMN regulation. Our findings suggest that the commonly expressed genes involved in regulation of multiple pathways were the underlying molecular mechanisms in the development of inflammatory, autoimmune, and hematologic diseases that share the common phenotypic characteristics of increased numbers of PMNs. Taken together, these data suggest that these genes are involved in the regulation of neutrophilia and that the corresponding gene products could serve as potential biomarkers and/or therapeutic targets for neutrophilia.