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Development of a label-free LC-MS/MS strategy to approach the identification of candidate protein biomarkers of disease recurrence in prostate cancer patients in a clinical trial of combined hormone and radiation therapy
Article first published online: 18 JUN 2013
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PROTEOMICS - Clinical Applications
Special Issue: Focus on Cancer Proteomics
Volume 7, Issue 5-6, pages 316–326, June 2013
How to Cite
Morrissey, B., O'Shea, C., Armstrong, J., Rooney, C., Staunton, L., Sheehan, M., Shannon, A. M. and Pennington, S. R. (2013), Development of a label-free LC-MS/MS strategy to approach the identification of candidate protein biomarkers of disease recurrence in prostate cancer patients in a clinical trial of combined hormone and radiation therapy. Prot. Clin. Appl., 7: 316–326. doi: 10.1002/prca.201300004
- Issue published online: 18 JUN 2013
- Article first published online: 18 JUN 2013
- Accepted manuscript online: 13 MAY 2013 06:25AM EST
- Manuscript Accepted: 16 APR 2013
- Manuscript Revised: 20 MAR 2013
- Manuscript Received: 17 JAN 2013
- St Luke's Institute of Cancer Research
- Clinical trial;
- Disease recurrence;
- Prostate cancer;
- Radiation therapy
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 (R2 = 0.85).
Conclusions and clinical relevance
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.