Untargeted metabolomics analysis of the urinary metabolic signature of acute and chronic gout

IF 3.2 3区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY
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Abstract

Background

Gout is a common kind of inflammatory arthritis with metabolic disorders. However, the detailed pathogenesis of gout is complex and not fully clear. We investigated the urine metabolic profiling of gout patients by ultra-performance liquid chromatograph quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS).

Method

Urine metabolites were extracted from 26 acute gout patients, 31 chronic gout patients, and 32 healthy controls. Metabolite extracts were analyzed by UPLC-Q-TOF-MS for untargeted metabolomics. The peak area of creatinine was used to correct the content variations of urine samples for the semi-quantitative analysis. The value of variable importance in the projection (VIP) was obtained through the orthogonal partial least squares-discrimination analysis (OPLS-DA), and several differential metabolites were screened out.

Results

The potential metabolic markers of gout in different stages were found based on the t-test. Finally, 18 different metabolites were identified through Human Metabolome Database (HMDB) and Targeted-MS/MS. The receiver operating characteristic (ROC) curve results revealed that all the screened biomarkers exerted high accuracy and diagnostic value. Pathway analysis indicated that the significantly different metabolites were mainly involved in purine metabolism and amino acid metabolism.

Conclusion

The identified potential biomarkers are mainly involved in purine metabolism and amino acid metabolism, which leads us to further explore the pathogenesis of gout. This will lead us to further explore the pathogenesis of gout and provide the basis and ideas for the prevention and treatment of gout.

对急性和慢性痛风尿液代谢特征的非靶向代谢组学分析
背景痛风是一种常见的伴有代谢紊乱的炎症性关节炎。然而,痛风的具体发病机制复杂且不完全清楚。我们采用超高效液相色谱四极杆飞行时间质谱(UPLC-Q-TOF-MS)对痛风患者的尿液代谢谱进行了研究。采用 UPLC-Q-TOF-MS 对代谢物提取物进行非靶向代谢组学分析。在半定量分析中,使用肌酐的峰面积来校正尿液样本的含量变化。通过正交偏最小二乘判别分析(OPLS-DA)获得了预测中的变量重要性值(VIP),并筛选出了几种差异代谢物。最后,通过人类代谢组数据库(HMDB)和靶向质谱(Targeted-MS/MS)鉴定出18种不同的代谢物。接受者操作特征曲线(ROC)结果显示,所有筛选出的生物标志物都具有很高的准确性和诊断价值。结论所发现的潜在生物标志物主要参与嘌呤代谢和氨基酸代谢,这将引导我们进一步探索痛风的发病机制。这将引导我们进一步探索痛风的发病机制,为痛风的预防和治疗提供依据和思路。
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来源期刊
Clinica Chimica Acta
Clinica Chimica Acta 医学-医学实验技术
CiteScore
10.10
自引率
2.00%
发文量
1268
审稿时长
23 days
期刊介绍: The Official Journal of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Clinica Chimica Acta is a high-quality journal which publishes original Research Communications in the field of clinical chemistry and laboratory medicine, defined as the diagnostic application of chemistry, biochemistry, immunochemistry, biochemical aspects of hematology, toxicology, and molecular biology to the study of human disease in body fluids and cells. The objective of the journal is to publish novel information leading to a better understanding of biological mechanisms of human diseases, their prevention, diagnosis, and patient management. Reports of an applied clinical character are also welcome. Papers concerned with normal metabolic processes or with constituents of normal cells or body fluids, such as reports of experimental or clinical studies in animals, are only considered when they are clearly and directly relevant to human disease. Evaluation of commercial products have a low priority for publication, unless they are novel or represent a technological breakthrough. Studies dealing with effects of drugs and natural products and studies dealing with the redox status in various diseases are not within the journal''s scope. Development and evaluation of novel analytical methodologies where applicable to diagnostic clinical chemistry and laboratory medicine, including point-of-care testing, and topics on laboratory management and informatics will also be considered. Studies focused on emerging diagnostic technologies and (big) data analysis procedures including digitalization, mobile Health, and artificial Intelligence applied to Laboratory Medicine are also of interest.
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