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Metabolomics analysis reveals four biomarkers associated with the gouty arthritis progression in patients with sequential stages

医学 代谢组学 生物标志物 内科学 接收机工作特性 痛风 生物信息学 生物化学 生物 化学
作者
Shang Lyu,Yi Rao,Peng Liu,Shilin Yang,Wanyuan Chen,Huajie Yang,Shiwen Ke,Hui Ouyang,Mingzhen He,Yulin Feng
出处
期刊:Seminars in Arthritis and Rheumatism [Elsevier BV]
卷期号:55: 152022-152022 被引量:10
标识
DOI:10.1016/j.semarthrit.2022.152022
摘要

The gouty arthritis (GA) progression was multistage, yet the GA clinical diagnosis guidelines were more inclined to suitable for acute gouty arthritis (AGA), thus neglecting of the progress of GA. This study aimed to identify specific biomarkers that were competent for reflecting the progression of GA and attempted to provide evidence for seasonable intervention of appropriate clinical treatment.A total of 547 patients with GA at sequential stages and healthy volunteers were divided into a training set (n = 347) and a validation set (n = 200). Serum metabolic profiles were determined by UHPLC-QTOF-MS-MS untargeted metabolomics, and biomarkers were identified by logistic regression and receiver operating characteristic analysis. Further, UHPLC-QE-MS was applied for accurate quantitative validation of identified potential biomarkers in the validation set samples.After serum metabolic profiles analysis by untargeted metabolomics, 12 metabolites with monotonous change trend were screened, and were verified by targeted metabolomics subsequently. The quantitative results showed the serum concentration of kynurenic acid(KYNA), N1-Methyl-2-pyridone-5-carboxamide(2PY), DL-2-Aminoadipic acid(2AMIA) and 5-hydroxyindole acetic acid(5-HIAA) of patients with sequential stages showed a strictly monotonic trend, and AUC was 0.97, 0.97, 0.96 and 0.95, respectively.KYNA and 5-HIAA are related to acute inflammation of GA, while 2PY and 2AMIA are related to renal function damage caused by long-term HUA. Therefore, we believe it is inappropriate to use a single biomarker to define the phase of GA. Actually, four biomarkers obtained in this paper should be integratedly adopted to evaluate the progression of GA with sequential stages.
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