Identification Of Differentially Expressed Key Genes And Pathways In Neutrophilia By Bioinformatics Analyses

Background: Increasing the number of neutrophil is essential to attack the invading pathogens,while improperly increasing the number of neutrophil in tissues may cause unnecessary tissue damage.Researching the changes of key genes and pathways in neutrophilia may provide a theoretical basis for elucidation of the pathogenesis of inflammatory diseases,some immunological and hematological diseases.objective: To identify key genes and pathways related to pathogenicity in neutrophils of patients with neutrophilia.Methods: Firstly,we screened and downloaded a total of 49 experimental and 22 control samples from Gene Expression Omnibus(GEO)datasets GSE64457,GSE94923,GSE54644,including septic shock patients,health neutrophil samples stimulated by GM-CSF or PKA agonist,polycythemia vera patients respectively.Secondly,we identified differentially expressed genes(DEGs)via the limma package in R,and then performed hierarchical clustering analysis.Thirdly,through intersecting DEGs from up-regulated and down-regulated DEGs group of every two datasets,we had gotten110 up-regulated and 108 down-regulated DEGs as candidate DEGs,and subsequently conducted gene ontology and pathway Enrichment Analysis,PPI network analysis and hub gene analysis,using multiple methods containing DAVID,PATHER,Reactome,STRING,ReactomeFIPlugInand Cytohubba in Cytoscape.Results: We had identified most significant hub DEGs,including AKT1,MAPK14,JAK1,EGR1,TLR4,CNOT6 L,CD44,LDLR,ENO1,ARRB1,IL6 ST,GAB1,MAP2K6.In addition,the intersection of DEGs from those three datasets includes 13 upregulated DEGs containing IL18R1?ATP13A3?CD44?LAIR1?ATP6V1C1?ATP11B?ADAM9?IL6ST?LDLR?EXOSC4?IL18RAP?PPA2?HES1and 5 down-regulated DEGs containing FCMR?SET?NOV?FGL2?TSPAN13.Besides,the pathways,such as interleukin-mediated signaling pathway,lipopolysaccharide-mediated signaling pathway,TNF signaling pathway,Toll-Like Receptors Cascades,MAPK signaling pathway,PI3K-Akt signaling pathway and the biological processes or molecular functions,such as apoptotic process,protein phosphorylation,intracellular signal transduction,kinase activity,catalytic activity and transferase activity were involved in neutrophilia.Conclusion:The hub genes found by this study might cause neutrophil increasing and implicate in the pathogenesis of inflammatory diseases,some autoimmune and hematological diseases through a variety of signaling pathways.These findings provide new sights into the foundation for selection of targets related to diagnosis,treatment and prognosis of those diseases.