Abstract

Development of a Blood Based Protein Signature to Stratify Patients for Prostate Cancer Treatment. From Discovery to Clinical Diagnostics

Stephen Pennington, Professor, University College Dublin

Prostate cancer is the most common cancer diagnosed and the second most common cause of cancer-related deaths in men in the Western world. Currently, serum prostate-specific antigen widely used biomarker for the diagnosis and management of patients with prostate cancer. However, it lacks performance adequately diagnose prostate cancer and is not effective for guiding key treatment decisions. We have used label-free LC-MS/MS to identify candidate biomarker proteins and established a panel of 64 proteins that was assembled using this data as well as data from previous gel-based proteomics studies and the literature. Using Skyline, a multiple reaction monitoring (MRM) assay was developed for 31 of these proteins and its reproducibility established on replicates of affinity depleted and crude serum samples. An initial verification of the 31 protein MRM assay on 63 independent prostate cancer serum samples demonstrated the robustness of the assay and random forest analysis of the data revealed that it has a favorable predictive performance for discriminating organ confined from non-organ confined prostate cancer. We are currently developing this assay for clinical use to support prostate cancer patient treatment decisions.