PDGFB, a new candidate plasma biomarker for venous thromboembolism: results from the VEREMA affinity proteomics study
PDGFB, a new candidate plasma biomarker for venous thromboembolism: results from the VEREMA affinity proteomics study
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DOI：
10.1182/blood-2016-05-711846
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发表时间：
2016-12-08
期刊：
影响因子：
20.3
通讯作者：
Odeberg, Jacob
中科院分区：
文献类型：
--
作者：
Bruzelius, Maria;Iglesias, Maria Jesus;Odeberg, Jacob
临床显然需要高特异性血浆生物标志物来预测静脉血栓栓塞 (VTE) 的风险，但迄今为止，此类标志物仍然难以捉摸。利用人类蛋白质图谱项目的亲和试剂和多重免疫测定，我们广泛分析了两项单独研究的血浆样本，以确定与 VTE 风险相关的候选蛋白质标记。我们使用由 755 种针对 408 种候选蛋白的抗体组成的悬浮珠阵列，筛选了 88 名 VTE 病例和 85 名匹配对照者的血浆样本，这些样本是瑞典“静脉血栓栓塞生物标志物研究”的一部分。我们发现，VTE 的发生与人类免疫缺陷病毒 I 型增强子结合蛋白 1 (HIVEP1)、冯维勒布兰德因子 (VWF)、谷胱甘肽过氧化物酶 3 (GPX3) 和血小板衍生生长因子 β (PDGFB) 的血浆水平之间存在显着关联。为了进行复制，我们分析了法国 FARIVE 研究中 580 例病例和 589 例对照的血浆样本。经过多次测试校正后，这些结果证实了 VWF 和 PDGFB 与 VTE 的关联，而 HIVEP1 和 GPX3 只观察到微弱的趋势。尽管 VWF 和 PDGFB 的血浆水平彼此之间存在适度相关（rho 类似于 0.30），但它们与 FARIVE 联合模型中的 VTE 风险独立相关（VWF P < .001；PDGFB P = .002）。血小板衍生生长因子。通过免疫捕获质谱和夹心酶联免疫吸附测定验证为捕获抗体的靶标。总之，我们证明高通量亲和血浆蛋白质组学分析是一种有价值的研究策略，可识别血栓形成相关疾病的潜在候选生物标志物，并且我们的研究表明 PDGFB 血浆水平与 VTE 存在新的关联。
There is a clear clinical need for high-specificity plasma biomarkers for predicting risk of venous thromboembolism (VTE), but thus far, such markers have remained elusive. Utilizing affinity reagents from the Human Protein Atlas project and multiplexed immuoassays, we extensively analyzed plasma samples from 2 individual studies to identify candidate protein markers associated with VTE risk. We screened plasma samples from 88 VTE cases and 85 matched controls, collected as part of the Swedish "Venous Thromboembolism Biomarker Study," using suspension bead arrays composed of 755 antibodies targeting 408 candidate proteins. We identified significant associations between VTE occurrence and plasma levels of human immunodeficiency virus type I enhancer binding protein 1 (HIVEP1), von Willebrand factor (VWF), glutathione peroxidase 3 (GPX3), and platelet-derived growth factor beta (PDGFB). For replication, we profiled plasma samples of 580 cases and 589 controls from the French FARIVE study. These results confirmed the association of VWF and PDGFB with VTE after correction for multiple testing, whereas only weak trends were observed for HIVEP1 and GPX3. Although plasma levels of VWF and PDGFB correlated modestly (rho similar to 0.30) with each other, they were independently associated with VTE risk in a joint model in FARIVE (VWF P < .001; PDGFB P = .002). PDGF. was verified as the target of the capture antibody by immunocapture mass spectrometry and sandwich enzyme-linked immunosorbent assay. In conclusion, we demonstrate that high-throughput affinity plasma proteomic profiling is a valuable research strategy to identify potential candidate biomarkers for thrombosis-related disorders, and our study suggests a novel association of PDGFB plasma levels with VTE.