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采用数据非依赖采集质谱技术和抗体微阵列发现用于肺栓塞诊断和危险分层的血浆生物标志物。

Discovery of plasma biomarkers with data-independent acquisition mass spectrometry and antibody microarray for diagnosis and risk stratification of pulmonary embolism.

机构信息

Peking University Fifth School of Clinical Medicine, Beijing, China.

The Key Laboratory of Geriatrics, Beijing Institution of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.

出版信息

J Thromb Haemost. 2021 Jul;19(7):1738-1751. doi: 10.1111/jth.15324. Epub 2021 Apr 23.

DOI:10.1111/jth.15324
PMID:33825327
Abstract

BACKGROUND

Pulmonary embolism (PE) is a leading cause of cardiovascular mortality worldwide. Rapid and accurate diagnosis and risk stratification are crucial for timely treatment options, especially in high-risk PE.

OBJECTIVES

The study aims to profile the comprehensive changes of plasma proteomes in PE patients and identify the potential biomarkers for both diagnosis and risk stratification.

PATIENTS/METHODS: Based on the data-independent acquisition mass spectrometry and antibody array proteomic technology, we screened the plasma samples (13 and 32 proteomes, respectively) in two independent studies consisting of high-risk PE patients, non-high-risk PE patients, and healthy controls. Some significantly differentially expressed proteins were quantified by ELISA in a new study group with 50 PE patients and 26 healthy controls.

RESULTS

We identified 207 and 70 differentially expressed proteins in PE and high-risk PE. These proteins were involved in multiple thrombosis-associated biological processes including blood coagulation, inflammation, injury, repair, and chemokine-mediated cellular response. It was verified that five proteins including SAA1, S100A8, TNC, GSN, and HRG had significant change in PE and/or in high-risk PE. The receiver operating characteristic curve analysis based on binary logistic regression showed that the area under the curve (AUC) of SAA1, S100A8, and TNC in PE diagnosis were 0.882, 0.788, and 0.795, and AUC of S100A8 and TNC in high-risk PE diagnosis were 0.773 and 0.720.

CONCLUSION

As predictors of inflammation or injury repair, SAA1, S100A8, and TNC are potential plasma biomarkers for the diagnosis and risk stratification of PE.

摘要

背景

肺栓塞(PE)是全球心血管死亡的主要原因。快速、准确的诊断和风险分层对于及时选择治疗方案至关重要,尤其是在高危 PE 中。

目的

本研究旨在分析 PE 患者血浆蛋白质组的综合变化,并确定潜在的诊断和风险分层生物标志物。

患者/方法:基于非依赖数据采集的质谱和抗体阵列蛋白质组学技术,我们在两项独立研究中筛选了高危 PE 患者、非高危 PE 患者和健康对照者的血浆样本(分别为 13 和 32 个蛋白质组)。在一个新的研究组中,使用 50 例 PE 患者和 26 例健康对照者的血浆样本,通过 ELISA 对一些差异显著的蛋白质进行了定量分析。

结果

我们在 PE 和高危 PE 中分别鉴定出 207 和 70 个差异表达蛋白。这些蛋白参与了多个与血栓形成相关的生物学过程,包括血液凝固、炎症、损伤、修复和趋化因子介导的细胞反应。研究验证了 SAA1、S100A8、TNC、GSN 和 HRG 这 5 种蛋白在 PE 和/或高危 PE 中发生了显著变化。基于二项逻辑回归的受试者工作特征曲线分析显示,SAA1、S100A8 和 TNC 在 PE 诊断中的曲线下面积(AUC)分别为 0.882、0.788 和 0.795,S100A8 和 TNC 在高危 PE 诊断中的 AUC 分别为 0.773 和 0.720。

结论

SAA1、S100A8 和 TNC 作为炎症或损伤修复的预测因子,是潜在的用于 PE 诊断和风险分层的血浆生物标志物。

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