In:
Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-9-7)
Abstract:
Although Leflunomide (LEF) is effective in treating rheumatoid arthritis (RA), there are still a considerable number of patients who respond poorly to LEF treatment. Till date, few LEF efficacy-predicting biomarkers have been identified. Herein, we explored and developed a DNA methylation-based predictive model for LEF-treated RA patient prognosis. Methods Two hundred forty-five RA patients were prospectively enrolled from four participating study centers. A whole-genome DNA methylation profiling was conducted to identify LEF-related response signatures via comparison of 40 samples using Illumina 850k methylation arrays. Furthermore, differentially methylated positions (DMPs) were validated in the 245 RA patients using a targeted bisulfite sequencing assay. Lastly, prognostic models were developed, which included clinical characteristics and DMPs scores, for the prediction of LEF treatment response using machine learning algorithms. Results We recognized a seven-DMP signature consisting of cg17330251, cg19814518, cg20124410, cg21109666, cg22572476, cg23403192, and cg24432675, which was effective in predicting RA patient’s LEF response status. In the five machine learning algorithms, the support vector machine (SVM) algorithm provided the best predictive model, with the largest discriminative ability, accuracy, and stability. Lastly, the AUC of the complex model(the 7-DMP scores with the lymphocyte and the diagnostic age) was higher than the simple model (the seven-DMP signature, AUC:0.74 vs 0.73 in the test set). Conclusion In conclusion, we constructed a prognostic model integrating a 7-DMP scores with the clinical patient profile to predict responses to LEF treatment. Our model will be able to effectively guide clinicians in determining whether a patient is LEF treatment sensitive or not.
Type of Medium:
Online Resource
ISSN:
1664-3224
DOI:
10.3389/fimmu.2023.1173187
DOI:
10.3389/fimmu.2023.1173187.s001
DOI:
10.3389/fimmu.2023.1173187.s002
DOI:
10.3389/fimmu.2023.1173187.s003
DOI:
10.3389/fimmu.2023.1173187.s004
DOI:
10.3389/fimmu.2023.1173187.s005
DOI:
10.3389/fimmu.2023.1173187.s006
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2023
detail.hit.zdb_id:
2606827-8
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