Verification of a Blood-Based Targeted Proteomics Signature for Malignant Pleural Mesothelioma.
Verification of a Blood-Based Targeted Proteomics Signature for Malignant Pleural Mesothelioma.
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DOI：
10.1158/1055-9965.epi-20-0543
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发表时间：
2020-10
期刊：
影响因子：
--
通讯作者：
Carbone DP
中科院分区：
文献类型：
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作者：
Cerciello F;Choi M;Sinicropi-Yao SL;Lomeo K;Amann JM;Felley-Bosco E;Stahel RA;Robinson BWS;Creaney J;Pass HI;Vitek O;Carbone DP
我们已经验证了一种基于质谱（MS）的靶向蛋白质组学特征，用于从血液中检测恶性胸膜间皮瘤（MPM）。在先前的独立研究中，通过血清中的靶向蛋白质组学鉴定了七肽生物标志物MPM签名。在这里，我们已经验证了该签名的简化版本的预测准确性，该签名现在由六肽生物标志物组成。我们应用液相色谱选择反应监测（LC-SRM），也称为多反应监测（MRM），对来自美国，澳大利亚和欧洲的213名MPM患者和189名无癌石棉暴露供体的402份血清样本进行了调查。组成特征的每个生物标志物是独立的信息，彼此没有明显的功能或物理关系。MS蛋白质组学提供的多重可能性允许它们整合到单个特征中，具有比单独的单个生物标志物更高的鉴别能力。该策略允许以这种方式增加其对临床决策的潜在效用。该签名区分MPM患者和石棉暴露供体，AUC为0.738。早期MPM的AUC为0.765。该特征也具有预后性，Kaplan-Meier分析显示高风险组和低风险组之间存在显著差异，风险比（HR）为1.659（95% CI [1.075，2.562]，P = 0.021）。靶向蛋白质组学允许从血液中开发具有MPM诊断和预后潜力的多分析物签名。蛋白质组特征代表了一种额外的诊断方法，用于为MPM风险患者提供临床决策。
We have verified a mass spectrometry (MS) based targeted proteomics signature for the detection of malignant pleural mesothelioma (MPM) from the blood. A seven-peptide biomarker MPM signature by targeted proteomics in serum was identified in a previous independent study. Here, we have verified the predictive accuracy of a reduced version of that signature, now composed of six-peptide biomarkers. We have applied liquid chromatography-selected reaction monitoring (LC-SRM), also known as multiple reaction monitoring (MRM), for the investigation of 402 serum samples from 213 MPM patients and 189 cancer-free asbestos exposed donors from the USA, Australia and Europe. Each of the biomarkers composing the signature was independently informative with no apparent functional or physical relation to each other. The multiplexing possibility offered by MS proteomics allowed their integration into a single signature with a higher discriminating capacity than that of the single biomarkers alone. The strategy allowed in this way to increase their potential utility for clinical decisions. The signature discriminated MPM patients and asbestos exposed donors with AUC of 0.738. For early stage MPM AUC was 0.765. This signature also was prognostic and Kaplan-Meier analysis showed a significant difference between high and low risk groups with a hazard ratio (HR) of 1.659 (95% CI [1.075, 2.562], P = 0.021). Targeted proteomics allowed the development of a multi-analyte signature with diagnostic and prognostic potential for MPM from the blood. The proteomic signature represents an additional diagnostic approach for informing clinical decisions for patients at risk for MPM.