Peptidomic analysis of endogenous plasma peptides from patients with pancreatic neuroendocrine tumours.
Peptidomic analysis of endogenous plasma peptides from patients with pancreatic neuroendocrine tumours.
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DOI：
10.1002/rcm.8183
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发表时间：
2018-08-30
期刊：
影响因子：
--
通讯作者：
Gribble FM
中科院分区：
文献类型：
--
作者：
Kay RG;Challis BG;Casey RT;Roberts GP;Meek CL;Reimann F;Gribble FM
胰腺神经内分泌肿瘤的诊断需要使用多个血浆等分试样，通过多种免疫分析对患者血浆进行研究。基于质谱技术的应用可以降低诊断所需的血浆成本和数量。使用已建立的基于乙腈的血浆肽富集策略提取两名胰腺神经内分泌肿瘤患者的血浆样本。使用纳米和高流速液相色谱/质谱 (LC/MS) 分析对循环肽组进行表征。为了评估该分析方法的诊断潜力，使用 10 分钟 LC/MS 肽筛选对来自对照受试者的大样本批次（68 份血浆）以及来自患有两种不同类型胰腺神经内分泌肿瘤（胰岛素瘤和胰高血糖素瘤）的受试者的等分试样进行了分析。非靶向血浆肽组学方法鉴定了源自胰高血糖素激素原、嗜铬粒蛋白 A、嗜铬粒蛋白 B 和其他与控制肽分泌相关的肽激素和蛋白质的肽。将检测到的胰高血糖素激素原衍生肽与使用针对胰高血糖素肽的多个抗体对鉴定的推定肽进行比较。比较血浆样品中所选肽的相对水平显示胰高血糖素瘤与胰岛素瘤和对照样品之间有明显的分离。有机溶剂提取方法与高流速分析的结合有可能用于帮助诊断和监测功能性胰腺神经内分泌肿瘤患者的治疗。然而，在将该方法应用于临床之前，需要进行大量验证。
Diagnosis of pancreatic neuroendocrine tumours requires the study of patient plasma with multiple immunoassays, using multiple aliquots of plasma. The application of mass spectrometry based techniques could reduce the cost and amount of plasma required for diagnosis. Plasma samples from two patients with pancreatic neuroendocrine tumours were extracted using an established acetonitrile‐based plasma peptide enrichment strategy. The circulating peptidome was characterised using nano and high flow rate liquid chromatography/mass spectrometry (LC/MS) analyses. To assess the diagnostic potential of the analytical approach, a large sample batch (68 plasmas) from control subjects, and aliquots from subjects harbouring two different types of pancreatic neuroendocrine tumour (insulinoma and glucagonoma), were analysed using a 10‐min LC/MS peptide screen. The untargeted plasma peptidomics approach identified peptides derived from the glucagon prohormone, chromogranin A, chromogranin B and other peptide hormones and proteins related to control of peptide secretion. The glucagon prohormone derived peptides that were detected were compared against putative peptides that were identified using multiple antibody pairs against glucagon peptides. Comparison of the plasma samples for relative levels of selected peptides showed clear separation between the glucagonoma and the insulinoma and control samples. The combination of the organic solvent extraction methodology with high flow rate analysis could potentially be used to aid diagnosis and monitor treatment of patients with functioning pancreatic neuroendocrine tumours. However, significant validation will be required before this approach can be clinically applied.
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