Analysis Of The Key Genes And Immune Infiltration Characteristics Of Rheumatoid Arthritis Synovium Based On Bioinformatics

Objective: The purpose of this study was to explore the key genes of rheumatoid arthritis(RA)synovium with bioinformatics analysis,and analyze the molecular functions and pathways,the relationship with immune cell infiltration and diagnostic value correlated with the key genes.Methods: Using the gene expression dataset of RA synovial tissue published in the GEO database,WGCNA and differential expression genes analysis were performed to retrieve the co-differentially expressed genes using the R language.A PPI network was obtained using STRING database,and key genes were discovered by using Cytoscape.The biological functions and enriched pathways associated with key genes were mined by conducting GO/KEGG and GSEA analysis.ROC curve was used to verify the diagnostic efficacy of the key genes.Finally,the immune-related key genes were screened by combining the Immport database.The correlations between the immune-related key genes and the enrichment level of the infiltrated immune cells and immune functions were evaluated by ss GSEA and Spearman correlation analysis.Results: In this study,eight key genes(PTPRC,TYROBP,ITGAM,LCP2,ITGB2,CD86,PLEK,HCK)related to RA synovium were screened by bioinformatics analysis.They are related to immunity and inflammation in enriched functions and pathways,and have high diagnostic value for RA.Functional enrichment analysis showed that the molecular functions of these key genes were mainly concentrated in opsonin binding,complement binding and amyloid-beta binding and other functions,as well as plasma membrane,secretory granular membrane,focal adhesion and other structures in cell composition.The biological processes involved by key genes are mainly related to the immune response,leukocyte activation,phagocytosis and positive regulation of cell activation.Pathway enrichment analysis showed that key genes were enriched in Rap1 signal pathway,cell adhesion molecules,bacterial and virus infection,natural killer cell-mediated cytotoxicity,complement and coagulation cascades,rheumatoid arthritis and other pathways.The area under the ROC-curve revealed that the key genes have high diagnostic value for rheumatoid arthritis(AUC>0.8),and are potential biomarkers and therapeutic targets for RA.Among them,PTPRC,TYROBP,LCP2,ITGB2,CD86 and HCK are immune-related key genes.The expression levels of them are closely related to the infiltration of various immune cells in synovium,such as B cells,CD8+T cells,macrophages,neutrophils,plasmacytoid dendritic cell,T helper cells,follicular helper T cells,regulatory T cells,and immune functions,such as inflammation promoting,human leukocyte antigen,and cytolytic activity,providing potential targets for immunotherapy of rheumatoid arthritis.Conclusions: This study identified the key genes of RA synovium,which not only provides a reliable biomarker for the diagnosis of RA,but also provides a new direction for exploring the immunotherapy of RA with multiple targets and pathways.