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. Issue 5 (18th June 2013)

• Record Type: Journal Article
• Authors: Morrissey, Brian; O'Shea, Carmel; Armstrong, John; Rooney, Cathy; Staunton, Lisa; Sheehan, Martina; Shannon, Aoife M.; Pennington, Stephen R.; Semmes, O. John; Conrads, Thomas P.
• Is Part Of: Proteomics. Volume 7:Issue 5/6(2013)
• Page Start: 316
• Page End: 326
• Publication Date: 2013-06-18
• Subjects: Proteomics -- Periodicals; 572.605
• DOI: 10.1002/prca.201300004
• Languages: English
• ISSNs: 1862-8346

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="prca1474-sec-0010" sec-type="section"> <title>Purpose</title> <p>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.</p> </sec> <sec id="prca1474-sec-0020" sec-type="section"> <title>Experimental design</title> <p>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.</p> </sec> <sec id="prca1474-sec-0030" sec-type="section"> <title>Results</title> <p>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 (<italic>P</italic> ≤ 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 (<italic>R</italic><sup>2</sup> = 0.85).</p> </sec> <sec id="prca1474-sec-0040" sec-type="section"> <title>Conclusions and clinical relevance</title> <p>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.</p> </sec> </abstract>