Determining the N-Glycan and Collagen/ Extracellular Matrix Protein Compositions in a Novel Outcome Cohort of Prostate Cancer Tissue Microarrays Using MALDI-MSI

Prostate cancer is a significant health concern, with metastasis posing major clinical challenges and resulting in poor patient outcome. Despite screening and treatment advances, a critical need for novel biomarkers to predict prostate cancer progression at the time of prostatectomy persists. Here, we assessed aberrant N-glycosylation patterns and alterations in extracellular matrix (ECM) proteins as potential biomarkers of predicting prostate cancer severity in a unique patient outcome cohort. Tissue microarray slides were assembled from primary prostatectomy specimens that were categorized into “no evidence of disease (NED)” and “metastasis (MET)” designations based on >5-year disease progression outcomes. Serial mass spectrometry imaging techniques were performed to analyze N-glycans and ECM components in formalin-fixed paraffin-embedded cores. The results revealed a significant upregulation of bisecting and multiantennary core-fucosylated N-glycans in MET tissues when compared with NED tissues. Alterations in ECM composition in both NED and MET cohorts were observed, particularly in collagen species and the amount of hydroxyproline content. Results suggest a coordinated alteration of ECM protein and glycosylation content in prostate cancer tissues can be predictive for postprostatectomy disease progression. Significance: Using matrix-assisted laser desorption/ionization mass spectrometry imaging techniques on a unique cohort of prostate cancer tissues, we highlighted several molecular characteristics of matrix that have potential to act as early predictors of prostate cancer metastasis.