Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland.
Proteomics Clin Appl. 2013 Jun;7(5-6):316-26. doi: 10.1002/prca.201300004.
Combined hormone and radiation therapy (CHRT) is one of the principle curative regimes for localised prostate cancer (PCa). Following treatment, many patients subsequently experience disease recurrence however; current diagnostics tests fail to predict the onset of disease recurrence. Biomarkers that address this issue would be of significant advantage.
Label-free LC-MS/MS for protein biomarker discovery and MRM for targeted confirmation were applied to patient serum samples accrued in a non-interventional clinical trial of CHRT.
Analysis of time-matched patient samples from a patient with disease recurrence compared with a time match disease-free individual supported the identification of 287 proteins. Of these, 141 proteins were quantified, 95 proteins changed in their expression (P ≤ 0.05 and ≥1.5-fold change) and of these 16 were selected for MRM confirmation. The protein expression changes observed in the label-free LC-MS/MS and MRM analysis were found to be highly correlated (R(2) = 0.85).
The establishment of a clinical trial to support the acquisition of samples and development of a pipeline for MS-based biomarker discovery and validation should contribute to the identification of a serum protein signature to predict or monitor the outcome of treatment of patients with PCa.
联合激素和放射治疗（CHRT）是局部前列腺癌（PCa）的主要治疗方案之一。治疗后，许多患者随后会出现疾病复发，但目前的诊断测试未能预测疾病复发的发生。能够解决这个问题的生物标志物将具有重要优势。
应用无标记 LC-MS/MS 进行蛋白质生物标志物发现和 MRM 进行靶向确认，对非干预性 CHRT 临床试验中累积的患者血清样本进行分析。
对一名疾病复发患者与一名时间匹配的无疾病个体的患者样本进行时间匹配分析，支持鉴定出 287 种蛋白质。其中，有 141 种蛋白质被定量，95 种蛋白质的表达发生变化（P ≤ 0.05 和 ≥1.5 倍变化），其中 16 种被选择用于 MRM 确认。无标记 LC-MS/MS 和 MRM 分析中观察到的蛋白质表达变化高度相关（R(2) = 0.85）。
建立临床试验以支持样本采集以及建立基于 MS 的生物标志物发现和验证的工作流程，应有助于鉴定出预测或监测 PCa 患者治疗结果的血清蛋白质特征。
