N-Linked Fucosylated Glycans Are Biomarkers for Prostate Cancer with a Neuroendocrine and Metastatic Phenotype

Abstract

Prostate cancer is a heterogeneous disease with a spectrum of metastatic disease, thus advancing biomarker discovery and pro-pathology and outcomes ranging from indolent to lethal. Although viding insights into mechanisms underlying metastatic disease. there have been recent advancements in prognostic tissue biomarkers, limitations still exist. We leveraged matrix-assisted laser desorption/ionization imaging of formalin-fixed, paraffin embedded prostate cancer specimens to determine if N-linked glycans expressed in the extracellular matrix of lethal neuroendocrine N-Glycan Fucose prostate cancer were also expressed in conventional prostate adefucosylation (fucose score) nocarcinomas that were associated with poor outcomes. We found that N-glycan fucosylation was abundant in neuroendocrine prostate cancer as well as adenocarcinomas at the time of prostatectomy Primary that eventually developed recurrent metastatic disease. Analysis of tumor patient-derived xenografts revealed that this fucosylation signature Indolent Metastatic Neuroendocrine/ was enriched differently across metastatic disease organ sites, with adenocarcinoma adenocarcinoma small cell carcinoma the highest abundance in liver metastases. These data suggest that N-linked fucosylated glycans could be an early tissue biomarker for Metastasis poor prostate cancer outcomes. Implications: These studies identify that hyper-fucosylated Node Bone N-linked glycans are enriched in neuroendocrine prostate cancer Liver metastasis metastasis metastasis and conventional prostate adenocarcinomas that progress to Created with BioRender.com ►