Identification of Genes and Pathways of Nonsteroidal Anti-inflammatory Drugs acting on Synovia from Women with Knee Osteoarthritis by Bioinformatics Analysis

Abstract

Objective: Through the bioinformatics analysis, to identify the genes and pathways of nonsteroidal anti-inflammatory drugs(NSARDs) acting on synovia from women with knee osteoarthritis (KOA), and to provide reference for clinical application. Methods: We downloaded the gene microarray datasets with the accession number of GSE55457 and GSE55584 from the Gene Expression Omnibus (GEO; https://www.ncbi.nlm.nih.gov/geo/) database, including 5 untreated KOA patients, 9 NSARDs treated KOA patients and 2 patients without KOA The samples in the untreated KOA group and the NSARDs treated KOA group were used for main analysis. The samples in the untreated KOA group and the normal control group were used for cooperative analysis. Then we performed robust multi-array (RMA) normalization with affy R programming package. After that, differential expression genes (DEGs) in main analysis and cooperative analysis were identified based on limma package separately. Screening the common DEGs from main analysis and cooperative analysis. Enriched gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of DEGs were obtained through the Database for Annotation, Visualization and Integrated Discovery (DAVID). What's more, protein-protein interaction (PPI) network was constructed, and we identified modules of PPI network through Cytoscape to screen valuable targets. The value of gene expression fold change (FC) ≥1.4 or ≤1/1.4, and P <0.05 were used as the screening conditions. P <0.05 and Associated genes count>5 were used as the screening conditions.Results: There were 338 DEGs in main analysis. Among them, 211 genes were up-regulated and 127 genes were down-regulated. There were 7005 DEGs in cooperative analysis. Among them, 6952 genes were up-regulated and 53 genes were down-regulated. A total of 129 common DEGs were identified between main analysis and cooperative analysis. There are 2 biological processes, 3 cell components and 2 molecular functions for the enrichment of differentially expressed genes.Conclusion: NSARDs may play a certain role in synovia from women with KOA by regulating the mRNA expressions of il-6, TNFRSF11A and CSF1R, which may become one of the indicators for monitoring the efficacy of NSAIDs.