Abstract PO-094: Mass spectrometry imaging of N-glycans identifies racial discrepancies in human prostate tumors

Abstract

Abstract Prostate cancer is the most commonly diagnosed cancer in men worldwide. A critical knowledge gap in prostate cancer biology is the molecular events underlining higher incidence and mortality rate in Black men. Identifying molecular features that separate racial disparities is a critical step in prostate cancer research that could lead to predictive biomarkers and personalized therapy. N-linked glycosylation is a required co-translational event during protein folding that modulates many biological processes, such as cell adhesion, immune modulation, cell-matrix interactions, and cell proliferation. Recently, aberrant N-linked glycosylation has been reported in prostate cancers. However, the full clinical implications of dysregulated glycosylation in prostate cancer has yet to be explored. Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) is a new and innovative technique that combines mass spectrometry with imaging, enabling the detection of glycans with spatial distribution. Herein, we performed MALDI-MSI analysis to characterize the N-glycan profile from tissue microarrays of over 100 patient tumors banked at the University of Kentucky with over 10 years of follow-up data. Additionally, we performed MALDI-MSI analysis on large sections of prostate cancer to define the regional distribution of N-glycans within the tumor microenvironment. We successfully identified 46 unique glycans from readily available formalin-fixed paraffin-embedded prostate tissue, and found significant N- glycan dysregulation between benign and prostate tumor tissue across all patient groups. High mannose as well as tri- and tetra-antennary N-glycans were predominantly found in tumor tissue and correlate with increased tumor grade. Surprisingly, several species of N-glycans were profoundly different between early grade prostate tumors resected from White and Black patients. Further, these glycans predict opposing overall survival between White and Black patients with prostate cancer. These data suggest differential N-linked glycosylation underline the racial disparity of prostate cancer prognosis. Our study highlights the potential clinical applications of MALDI-MSI for digital pathology and biomarker applications, and reveals molecular features that contribute to the racial disparity in diagnosis and survival of prostate cancer patients. Citation Format: Lindsey R. Conroy, Lyndsay E.A. Young, Grant L. Austin, Alexanda E. Stanback, Derek B Allison, Matthew S. Gentry, Richard R. Drake, Ramon C. Sun. Mass spectrometry imaging of N-glycans identifies racial discrepancies in human prostate tumors [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-094.