Bioinformatics Analysis Screened and Identified Key Genes, miRNAs and TFs as Potential Biomarkers for Progression of Rheumatoid Arthritis

Elderly patients are prone to rheumatoid arthritis (RA), which may cause reduce quality of life. However, the molecular pathogenesis of RA has not been fully elucidated, and current treatments remain inadequate. Therefore, it is important to explore the molecular mechanism of RA. Next generation sequancing (NGS) data of RA (GSE274996) was obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) in cases of RA and normal controls, and the Gene Ontology (GO) and and REACTOME pathway enrichment analysis were performed using the DESeq2 R/Bioconductor software package and g:Profiler, respectively. Analysis and visualization of protein-protein interaction networks (PPI) were carried out with IID and Cytoscape. miRNA-hub gene regulatory network, TF-hub gene regulatory network and drug-hub gene interaction network were built by Cytoscape to predict the underlying microRNAs (miRNAs), transcription factors (TFs) and drugs associated with hub genes. The diagonstic value of hub genes were assessed by receiver operating characteristic curve (ROC). Total of 958 DEGs were identified between RA and normal control in GSE274996, including 479 up-regulated and 479 down-regulated genes. These genes were enriched in multicellular organismal process, cytosol, enzyme binding, signal transduction, organelle organization, membrane, electron transfer activity and metabolism. A total of hub genes were collected, including MYC, MKI67, MAPK6, HSPA9, ANLN, SQSTM1, ARRB1, RAC1, BSG and TRIM27, miRNAs were predicted including hsa-miR-5094, hsa-miR-20a-5p, hsa-miR-411-3p and hsa-miR-34c-5p, TFs were predicted including ESR1, FOS, EN1 and FOXL1 and 4 drugs molecules were predicted including Atorvastatin, Mefloquine, Oxprenolol and Acarbose. Evaluation of MYC, MKI67, MAPK6, HSPA9, ANLN, SQSTM1, ARRB1, RAC1, BSG, TRIM27, hsa-miR-5094, hsa-miR-20a-5p, hsa-miR-411-3p hsa-miR-34c-5p, ESR1, FOS, EN1 and FOXL1 as potential biomarkers can contribute to the subsequent theoretical analysis of potential molecular mechanisms and development of RA, so that the diagnosis of RA might be more accurate, and it is possible to provide therapeutic and prognostic medicine targets.