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

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.