Abstract
Background: Although rheumatoid arthritis (RA) is a common autoimmune disease, the precise pathogenesis of the disease remains unclear. Recent research has unraveled the role of autophagy in the development of RA. This research aims to explore autophagy-related diagnostic biomarkers in the peripheral blood of RA patients. Methods: The gene expression profiles of GSE17755 were retrieved from the gene expression ontology (GEO) database. Differentially expressed autophagy-related genes (DE-ARGs) were identified for the subsequent research by inserting autophagy-related genes and differentially expressed genes (DEGs). Three machine learning algorithms, including random forest, support vector machine recursive feature elimination (SVM-RFE), and least absolute shrinkage and selection operator (LASSO), were employed to identify diagnostic biomarkers. A nomogram model was constructed to assess the diagnostic value of the biomarkers. The CIBERSORT algorithm was performed to investigate the correlation of the diagnostic biomarkers with immune cells and immune factors. Finally, the diagnostic efficacy and differential expression trend of diagnostic biomarkers were validated in multiple cohorts containing different tissues and diseases. Results: In this study, 25 DE-ARGs were identified between RA and healthy individuals. In addition to "macroautophagy" and "autophagy-animal," DE-ARGs were also associated with several types of programmed cell death and immune-related pathways according to GO and KEGG analysis. Three diagnostic biomarkers, EEF2, HSP90AB1 and TNFSF10, were identified by the random forest, SVM-RFE, and LASSO. The nomogram model demonstrated excellent diagnostic value in GSE17755 (AUC = 0.995, 95% CI: 0.988-0.999). Furthermore, immune infiltration analysis showed a remarkable association between EEF2, HSP90AB1, and TNFSF10 expression with various immune cells and immune factors. The three diagnostic biomarkers also exhibited good diagnostic efficacy and demonstrated the same trend of differential expression in multiple validation cohorts. Conclusion: This study identified autophagy-related diagnostic biomarkers based on three machine learning algorithms, providing promising targets for the diagnosis and treatment of RA.