Team Project

PCA-3 Reference Set Application: Zhang/Johns Hopkins: Glycoprotein Biomarkers for the Early Detection of Aggressive Prostate Cancer

PCA3 Ref Set App: Zhang (2019)
Feng, ZidingFred Hutchinson Cancer Research Center
No design specified.
Prostate and Urologic Cancers Research Group

This project aims to determine the performance of using urinary glycoproteins for the early detection of aggressive prostate cancer (PCa). Using glycoproteomics and data-independent acquisition (DIA) mass spectrometry (MS), our previous study has demonstrated the development of glycoproteomic workflow for urine analysis and identified urinary glycoproteins associated aggressive prostate cancer (AG PCa) with Gleason 8 and plus compared to non-aggressive prostate cancer (NAG PCa) with Gleason 6. In this study, we propose to validate the clinical performance of these candidate glycoproteins for various clinical applications: for the early detection of AG PCa (Gleason 7 and plus) using urine samples from NCI-EDRNs Urinary PCA3 Evaluation Trial: as well as their capacity in predicting higher tumor grade at radical prostatectomy (RP) in the tissue biopsy Upgrading Study (URS). We will also develop ELISA urinary assays for 4 candidate glycoproteins and apply the ELISA assays to the urine specimens from PC3 trial and URS to evaluate the clinical performance and compare the performance with the results from DIA-MS analysis. If successful, the project may generate novel biomarkerbased prediction tools to assist patients making clinical decisions regarding diagnostic biopsy, prostatectomy, or active surveillance, and would likely reduce unnecessary treatment in patients with low-grade prostate cancers.

We propose the following two aims: 1. Determine the performance of using urinary glycoproteomics and mass spectrometry for the detection of aggressive prostate cancer. We will (a) validate 4 candidate glycoproteins to detect AG PCa in diagnostic biopsy in the NCI-EDRNs Urinary PCA3 Evaluation Trial: (b) with PCA3 trial samples further develop a glycoproteomic risk score for predicting AG Pca in diagnostic biopsy; (c) validate the utility of glycoproteins separately and in combination to predict prostate cancer with a higher tumor grade (i.e., Gleason 3+4 or greater) at radical prostatectomy with NCI-EDRN Tissue Upgrading cohort. 2. Develop and apply ELISA assays to verify the candidate glycoproteins as non-invasive urinary tests for detecting aggressive prostate cancer.

No datasets are currently associated with this protocol.

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