Identification Of Differentially Expressed Key Genes And Pathway In Peripheral Blood T Cells Of Patients With Multiple Sclerosis By Bioinformatics Analysis

Background: Multiple sclerosis(MS)is an autoimmune-mediated disease characterized by inflammatory demyelinating of the central nervous system.At present,the etiology and pathogenesis are not very clear,and it is currently incurable.Many studies have confirmed that adaptive immunity plays an important role in the pathogenesis of this disease and MS is mainly mediated by T cells.Researching the changes of key genes and pathways related to pathogenicity in peripheral blood T cells of patients with multiple sclerosis may provide theoretical basis for elucidating the pathogenesis of multiple sclerosis and other autoimmune and inflammatory diseases.objective: Identification of key genes and pathways related to pathogenicity in T cells of patients with multiple sclerosis.Methods:Firstly,we screened and downloaded a total of 42 experimental and 35 control peripheral blood T cell samples from Gene Expression Omnibus(GEO)transcriptome gene expression profile datasets GSE64457,GSE94923,GSE54644.Then,we also screened and downloaded miRNA expression dataset GSE43590 including T cell samples from 6 patients with multiple sclerosis and 6 healthy controls.Secondly,we identified differentially expressed genes(DEGs)via the limma package in R,andthen performed hierarchical clustering analysis and principal component analysis.Thirdly,through intersecting DEGs from up-regulated and down-regulated DEGs group of every two datasets in three transcriptome gene expression profile datasets,we had gotten 77 up-regulated and 61down-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,ReactomeFIPlugIn and Cytohubba in Cytoscape.Finally,we had predicted the miRNA-mRNA targeting relationship through using the starBase database and miRDB database.Results: We had identified most significant hub DEGs,including EIF4 E,RPL37A,RPS24,RPL31,EIF4G1,HIST2H2 BE,CCL5,NACA,SMC3,SRSF11,TPR,ZEB1,CCR2,HNRNPA0,OTUD1,PURA,and the more critical miRs,including miR-494-3p,miR-106b-5p,miR-15b-5p,miR-23b-3p,miR-29a-3p,miR-30b-5p,miR-30c-5p,miR-30d-5p,miR-320 d,miR-425-5p,and the top 20 key DEGs selected by miRNA-mRNA targeting relationship analysis are as follows: CDK6,AMMECR1,ETNK1,SPTBN1,USP46,RICTOR,ITPKB,TNFAIP3,DMXL1,EEA1,NRIP1,IRS2,UBE2V2,C10orf76,ANKRD12,SACS,ARRDC3,HNRNPA0,EIF4 E,SOCS3.Besides,the pathways,such as interleukin-10 signaling,inflammation mediated by chemokine and cytokine signaling pathway,adipocytokine signaling pathway,signalingby leptin,chemokine signaling pathway;and the biological processes,such as monocyte chemotaxis,neutrophil chemotaxis,positive regulation of natural killer cell chemotaxis,chemokine-mediated signaling pathway,viral transcription,positive regulation of T cell chemotaxis;and the molecular functions,such as RNA binding,CCR1 chemokine receptor binding,protein binding,CCR5 chemokine receptor binding,poly(A)RNA binding,heat shock protein binding were involved in neutrophilia.Conclusion:The hub genes and miRNAs might cause multiple sclerosis through a variety of signaling pathways and implicate in the pathogenesis of multiple sclerosis.These findings provide new sights into the foundation for selection of targets related to diagnosis,treatment and prognosis of multiple sclerosis.