Identification of a seven glycopeptide signature for malignant pleural mesothelioma in human serum by selected reaction monitoring
Identification of a seven glycopeptide signature for malignant pleural mesothelioma in human serum by selected reaction monitoring
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DOI：
10.1186/1559-0275-10-16
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发表时间：
2013-01-01
影响因子：
3.8
通讯作者：
Wollscheid, Bernd
中科院分区：
文献类型：
--
作者：
Cerciello, Ferdinando;Choi, Meena;Wollscheid, Bernd
背景：血清生物标志物可以改善恶性胸膜间皮瘤（MPM）的诊断和治疗。然而，由于缺乏用于临床评估的检测技术，对潜在的新血清生物标志物候选物的评估受到阻碍。在这里，我们采用假设驱动的靶向蛋白质组学策略来鉴定和临床评估患者队列血清中MPM候选生物标志物。结果：基于细胞表面暴露的糖蛋白容易从肿瘤细胞释放到循环系统的假设，我们筛选了模型细胞系的表面组，以寻找潜在的MPM候选生物标志物。选择性反应监测（SRM）测定技术允许直接评估血清中新发现的候选物。我们在训练和独立验证集的背景下对51个候选生物标志物进行了评估，发现血清中MPM的可重复糖肽特征与MPM生物标志物间皮素互补。结论：我们的研究表明，SRM检测技术可以直接临床评估蛋白质衍生的候选生物标志物，而目前临床上可靠的ELISA技术还不存在。
Background: Serum biomarkers can improve diagnosis and treatment of malignant pleural mesothelioma (MPM). However, the evaluation of potential new serum biomarker candidates is hampered by a lack of assay technologies for their clinical evaluation. Here we followed a hypothesis-driven targeted proteomics strategy for the identification and clinical evaluation of MPM candidate biomarkers in serum of patient cohorts.Results: Based on the hypothesis that cell surface exposed glycoproteins are prone to be released from tumor-cells to the circulatory system, we screened the surfaceome of model cell lines for potential MPM candidate biomarkers. Selected Reaction Monitoring (SRM) assay technology allowed for the direct evaluation of the newly identified candidates in serum. Our evaluation of 51 candidate biomarkers in the context of a training and an independent validation set revealed a reproducible glycopeptide signature of MPM in serum which complemented the MPM biomarker mesothelin.Conclusions: Our study shows that SRM assay technology enables the direct clinical evaluation of protein-derived candidate biomarker panels for which clinically reliable ELISA's currently do not exist.