Differential urinary proteins to diagnose coronary heart disease based on iTRAQ quantitative proteomics

Differential urinary proteins to diagnose coronary heart disease based on iTRAQ quantitative proteomics
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基于iTRAQ定量蛋白质组学的差异尿蛋白诊断冠心病

DOI:
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发表时间:
2019
影响因子:
4.3
通讯作者:
Yong Zeng
Yong Zeng
中科院分区:
化学2区
文献类型:
--
作者:
Haidan Sun;Danqi Wang;Dongfang Liu;Zhengguang Guo;Chen Shao;Wei Sun;Yong Zeng

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冠状动脉疾病(CAD)是全身性动脉粥样硬化性疾病的一种表现。通过干预或传统的评分风险因素进行评估。诊断受到不准确和侵入性方法的限制。开发非侵入性方法来筛查CAD的风险是一个重大挑战。我们的目的是确定与CAD相关的尿蛋白。我们使用iTRAQ标记,然后使用2D LC-MS/MS比较CAD患者与健康队列的尿蛋白质组。采用多反应监测法(MRM)对差异蛋白进行验证。基于MRM数据的ROC分析用于评估诊断应用。共检测到876个蛋白质,发现100个差异蛋白质,功能分析表明,这些差异蛋白质主要与肝X受体/维甲酸X受体(LXR/RXR)通路激活、动脉粥样硬化信号传导、一氧化氮和活性氧的产生有关,IPA分析表明其上游调控因子为APOE。19个差异蛋白经MRM分析得到验证。基于MRM数据的ROC显示,两种蛋白(APOD和TFF 1)的组合可以诊断CAD,其敏感性为85%,特异性为99%(AUC 0.95)。尿蛋白质组可反映CAD的病理生理变化,可用于CAD的临床研究。
AbstractCoronary artery disease (CAD) is a manifestation of systemic atherosclerotic disease. It is assessed by intervention or traditional scoring risk factors. Diagnosis is limited by inaccurate and invasive methods. Developing noninvasive methods to screen for the risk of CAD is a major challenge. We aimed to identify urinary proteins associated with CAD. We utilized iTRAQ labeling followed by 2D LC-MS/MS to compare the urinary proteome of CAD patients to healthy cohorts. The multiple reaction monitoring (MRM) was used to verify the differential proteins. ROC analysis based on MRM data was used to evaluate the diagnostic application. A total of 876 proteins were quantified, and 100 differential proteins were found. Functional analysis revealed that the differential proteins were mainly associated with Liver X Receptor/Retinoid X Receptor (LXR/RXR) pathway activation, atherosclerosis signaling, production of nitric oxide and reactive oxygen species, and the top upstream regulator of the differential proteins by IPA analysis indicated to the APOE. Nineteen differential proteins were verified by MRM analysis. ROC based on MRM data revealed that the combination of two proteins (APOD and TFF1) could diagnose CAD with 85% sensitivity and 99% specificity (AUC 0.95). The urinary proteome might reflect the pathophysiological changes in CAD and be used for the clinical study of CAD.
DOI: 10.2741/4378
发表时间: 2016-01-01
期刊: Frontiers in bioscience (Landmark edition)
影响因子: --
作者:
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发表时间: 1994-01-01
期刊: ARTERIOSCLEROSIS AND THROMBOSIS
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发表时间: 2009
影响因子: 29.7
作者:
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通讯作者: Ley K