Potential biomarkers that discriminate rheumatoid arthritis and osteoarthritis based on the analysis and validation of datasets

Abstract

Background: Rheumatoid arthritis (RA) and osteoarthritis (OA) share some similar arthritic symptoms, but different mechanisms underlie the pathogenesis of these two diseases. Analysis of differentially expressed molecules in rheumatoid arthritis and osteoarthritis may assist in improving diagnosis and treatment strategies in clinical practice. Methods: Microarray and RNA-seq data were acquired from the gene expression omnibus database. Differentially expressed genes (DEGs) were identified using Bioconductor packages. Receiver operating characteristic curves were plotted to assess performance. Gene ontology enrichment analysis was conducted using the clusterProfiler application. During validation, synovial fluid was harvested from patients who had undergone in-hospital joint replacement, in which the expression of proteins was measured using enzyme-linked immunosorbent assays. Results: Compared with OA samples, RA samples showed 14 genes to be upregulated and 3 to be downregulated. Gene ontology analysis indicated that DEGs principally included molecules responsible for the regulation of a synovial tissue inflammatory response. Seven genes displayed a good discriminatory power with an AUC higher than 0.90. ADAMDEC1 was the biomarker that most clearly discriminated RA from OA in the database, exhibiting an AUC of 0.999, a sensitivity of 100%, and a specificity of 97.8%. Following validation, the expression levels of ADAMDEC1 in the synovial fluid from RA patients were significantly higher than those in the synovial fluid from OA patients (P < 0.05). At the cut-off value of 1957 pg/mL, ADAMDEC1 expression in the synovial fluid discriminated RA from OA with an AUC of 0.951, a specificity of 88.6%, and a sensitivity of 92.9%. Conclusion: The differential expression of genes in RA compared with OA indicates potential targets for molecular diagnosis and treatment. The presence of ADAMDEC1 in synovial fluid is a good biomarker of RA.