PSMA Glycosylation and Aggressive Prostate Cancer Progression
Abstract
Prostate cancer (PCa) is the most prevalent cancer among men and the second most common cause of cancer-related deaths in the United States. In 2017, it is estimated that there will be 161,360 new PCa cases and 26,730 deaths due to the disease in the USA. A major clinical challenge is the inability of current diagnostic tests to distinguish between aggressive and indolent tumors. Novel prognostic biomarkers that discriminate between aggressive and non-aggressive forms of PCa will provide major benefits to patients by assisting in the development of precision treatment for this susceptible patient population. In this application, we focus on differentiating between locally aggressive disease early enough in order to personalize treatment decisions. The objective is on differentiating significant versus non-significant disease by determining the expression profiles of glycans (sugar molecules) that are attached to prostate membrane-specific antigen (PSMA), a glycoprotein that is a validated target for the imaging and therapy of PCa. Changes in glycosylation patterns are of great significance, as these may influence oncogenesis. Aberrant glycosylation is often associated with aggressive disease progression. PSMA has 10 N-linked glycosylation sites; however, the status and expression profile of glycans is unknown, and the role of N-linked glycosylation in prostate cancer progression is unknown. In this application, we focus on differentiating between significant versus non-significant prostate cancer disease using post-DRE urine samples. The analysis of PSMA glycoforms in these prostate proximal body fluids will provide new information on the role of PSMA glycosylation in prostate cancer progression. We will also determine whether qualitative and quantitative differences in glycans and glycopeptides from PSMA in the two sample cohorts can be used to discriminate between patients with significant versus non-significant disease. These results may provide the basis for improved prostate cancer prognosis and a significant impact in detecting aggressive disease early enough in order to personalize treatment decisions.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810228
Entities
People
- Julius O Nyalwidhe
Organizations
- Eastern Virginia Medical School
- United States Army