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定量尿蛋白质组分析揭示了 Behcet 病葡萄膜炎疾病活动的潜在生物标志物。

Quantitative urinary proteome analysis reveals potential biomarkers for disease activity of Behcet's disease uveitis.

机构信息

Department of Anesthesiology, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, 266071, China.

Beijing Key Laboratory of Gene Engineering Drug and Biotechnology, College of Life Sciences, Beijing Normal University, Beijing100875, China.

出版信息

BMC Ophthalmol. 2024 Jul 9;24(1):277. doi: 10.1186/s12886-024-03557-9.

Abstract

PURPOSE

Behçet's disease-associated uveitis (BDU) is a severe, recurrent inflammatory condition affecting the eye and is part of a systemic vasculitis with unknown etiology, making biomarker discovery essential for disease management. In this study, we intend to investigate potential urinary biomarkers to monitor the disease activity of BDU.

METHODS

Firstly, label-free data-dependent acquisition (DDA) and tandem mass tag (TMT)-labeled quantitative proteomics methods were used to profile the proteomes of urine from active and quiescent BDU patients, respectively. For further exploration, the remaining fifty urine samples were analyzed by a data-independent acquisition (DIA) quantitative proteomics method.

RESULTS

Twenty-nine and 21 differential proteins were identified in the same urine from BDU patients by label-free DDA and TMT-labeled analyses, respectively. Seventy-nine differentially expressed proteins (DEPs) were significantly changed in other active BDU urine samples compared to those in quiescent BDU urine samples by IDA analysis. Gene Ontology (GO) and protein-protein interaction (PPI) analyses revealed that the DEPs were associated with multiple functions, including the immune and neutrophil activation responses. Finally, seven proteins were identified as candidate biomarkers for BDU monitoring and recurrence prediction, namely, CD38, KCRB, DPP4, FUCA2, MTPN, S100A8 and S100A9.

CONCLUSIONS

Our results showed that urine can be a good source of biomarkers for BDU. These dysregulated proteins provide potential urinary biomarkers for BDU activity monitoring and provide valuable clues for the analysis of the pathogenic mechanisms of BDU.

摘要

目的

贝切特病相关性葡萄膜炎(BDU)是一种严重的、复发性眼部炎症性疾病,属于系统性血管炎的一部分,病因不明,因此生物标志物的发现对于疾病的管理至关重要。在这项研究中,我们旨在探索潜在的尿液生物标志物来监测 BDU 的疾病活动。

方法

首先,采用无标记数据依赖采集(DDA)和串联质量标签(TMT)标记定量蛋白质组学方法分别对活动期和静止期 BDU 患者的尿液蛋白质组进行了分析。为了进一步探索,剩余的五十个尿液样本采用了一种非依赖性数据采集(DIA)定量蛋白质组学方法进行分析。

结果

无标记 DDA 和 TMT 标记分析分别在 BDU 患者的同一份尿液中鉴定出 29 个和 21 个差异蛋白。与静止期 BDU 尿液样本相比,通过 IDA 分析发现,79 个差异表达蛋白(DEPs)在其他活动期 BDU 尿液样本中显著改变。基因本体论(GO)和蛋白质-蛋白质相互作用(PPI)分析表明,这些 DEPs 与多种功能相关,包括免疫和中性粒细胞激活反应。最后,鉴定出 7 种蛋白质作为 BDU 监测和复发预测的候选生物标志物,即 CD38、KCRB、DPP4、FUCA2、MTPN、S100A8 和 S100A9。

结论

我们的结果表明,尿液可以作为 BDU 的良好生物标志物来源。这些失调的蛋白质为 BDU 活动监测提供了潜在的尿液生物标志物,并为 BDU 发病机制的分析提供了有价值的线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfba/11232131/cc263d56039b/12886_2024_3557_Fig1_HTML.jpg

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