Quantitative proteomic analysis by iTRAQ for identification of candidate biomarkers in plasma from acute respiratory distress syndrome patients
Quantitative proteomic analysis by iTRAQ for identification of candidate biomarkers in plasma from acute respiratory distress syndrome patients
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DOI：
10.1016/j.bbrc.2013.09.027
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发表时间：
2013-11-08
影响因子：
3.1
通讯作者：
Xi, Xiuming
中科院分区：
文献类型：
--
作者：
Chen, Xia;Shan, Qiang;Xi, Xiuming
急性呼吸窘迫综合征（ARDS）是危重患者发病和死亡的主要原因。对 ARDS 患者血浆进行蛋白质组学分析可以阐明用于诊断和病理生理学的新生物标志物，并确定潜在的 ARDS 治疗靶点。在这项研究中，我们招募了 26 名患者（15 名对照者，11 名 ARDS）。 ARDS组根据损伤类型分为两组：（1）直接肺损伤（AD）和（2）间接肺损伤（AI）。使用 iTRAQ（用于相对和绝对定量的同量异位标签）分析，我们鉴定了代表 132 种血浆蛋白的 2429 种肽。其中，16个在ARDS患者中存在差异表达，其中包括AI和AD组之间的11个重叠蛋白以及5个AI特异性蛋白。蛋白质注释显示，脂质转运和补体激活在生物过程类别中显着富集，脂质转运蛋白、转运蛋白和丝氨酸型肽酶活性在分子功能类别中显着富集。 IPA（Ingenuity Pathway Analysis）信号通路显示，重叠蛋白参与多种信号通路，包括那些潜在的急性期反应；肝脏 X 受体/类视黄醇 X 受体 (LXR/RXR) 和法尼醇 X (FXR)/RXR 激活；网格蛋白介导的内吞作用；动脉粥样硬化;白细胞介素（IL）-12；补体系统；以及巨噬细胞中细胞因子、一氧化氮和活性氧的产生。我们首次使用 iTRAQ 方法对 ARDS 血浆进行蛋白质组学分析。我们的数据提供了新的候选生物标志物，并揭示了 ARDS 潜在的病理机制。 (C) 2013 Elsevier Inc. 保留所有权利。
Acute respiratory distress syndrome (ARDS) is a major cause of morbidity and mortality in critical patients. Proteomic analysis of plasma from individuals with ARDS could elucidate new biomarkers for diagnosis and pathophysiology and identify potential ARDS treatment targets. In this study, we recruited 26 patients (15 controls, 11 ARDS). The ARDS group was subdivided into two groups depending on the type of injury: (1) direct lung injury (AD) and (2) indirect lung injury (AI). Using iTRAQ (isobaric tags for relative and absolute quantitation) analysis, we identified 2429 peptides representing 132 plasma proteins. Among these, 16 were differentially expressed in ARDS patients, including 11 overlapping proteins between the AI and AD group and 5 AI-specific proteins. Protein annotation revealed that lipid transport and complement activation were significantly enriched in the biological process category, and lipid transporter, transporter, and serine-type peptidase activities were significantly enriched in the molecular function category. IPA (Ingenuity Pathway Analysis) signaling pathways revealed that the overlapping proteins were involved in a variety of signaling pathways, including those underlying acute phase response; liver X receptor/retinoid X receptor (LXR/RXR) and farnesoid X (FXR)/RXR activation; clathrin-mediated endocytosis; atherosclerosis; interleukin (IL)-12; complement system; and cytokine, nitric oxide, and reactive oxygen species production in macrophages. We present the first proteomic analysis of ARDS plasma using the iTRAQ approach. Our data provide new biomarker candidates and shed light on potential pathological mechanisms underlying ARDS. (C) 2013 Elsevier Inc. All rights reserved.