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

• Published in: Proteomics. Clinical applications Vol. 7; no. 5-6; pp. 316 - 326
• Main Authors: Morrissey, Brian, O'Shea, Carmel, Armstrong, John, Rooney, Cathy, Staunton, Lisa, Sheehan, Martina, Shannon, Aoife M., Pennington, Stephen R.
• Format: Journal Article
• Language: English
• Published: Germany Blackwell Publishing Ltd 01.06.2013; Wiley Subscription Services, Inc
• Subjects: Antineoplastic Agents, Hormonal - therapeutic use; Biomarker; Biomarkers; Biomarkers, Tumor - blood; Blood Proteins - analysis; Blood Proteins - metabolism; Chromatography, High Pressure Liquid; Clinical trial; Clinical trials; Combined Modality Therapy; Disease recurrence; Humans; Male; Nanotechnology; Patients; Principal Component Analysis; Prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - radiotherapy; Proteins; Radiation therapy; Recurrence; Tandem Mass Spectrometry; Time Factors; Trypsin - metabolism
• ISSN: 1862-8346; 1862-8354
• DOI: 10.1002/prca.201300004

Purpose 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. Experimental design 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. Results 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.