N-Linked Fucosylated Glycans Are Biomarkers for Prostate Cancer with a Neuroendocrine and Metastatic Phenotype
Prostate cancer is a heterogeneous disease with a spectrum of pathology and outcomes ranging from indolent to lethal. Although 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 prostate cancer were also expressed in conventional prostate adenocarcinomas 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 that eventually developed recurrent metastatic disease. Analysis of patient-derived xenografts revealed that this fucosylation signature was enriched differently across metastatic disease organ sites, with the highest abundance in liver metastases. These data suggest that N-linked fucosylated glycans could be an early tissue biomarker for poor prostate cancer outcomes. Implications: These studies identify that hyper-fucosylated N-linked glycans are enriched in neuroendocrine prostate cancer and conventional prostate adenocarcinomas that progress to metastatic disease, thus advancing biomarker discovery and providing insights into mechanisms underlying metastatic disease.
Authors
- Dean A. Troyer (ORCID: https://orcid.org/0000-0002-0337-5890)
- Joseph E. Ippolito (ORCID: https://orcid.org/0000-0003-1913-5573)
- Nikolaos A. Trikalinos (ORCID: https://orcid.org/0000-0001-8611-2182)
- Eva Corey (ORCID: https://orcid.org/0000-0002-9244-3807)
- Anand S. Mehta (ORCID: https://orcid.org/0000-0002-9846-9389)
- Kaitlyn Bejar (ORCID: https://orcid.org/0000-0002-3911-9290)
- Cody Weimholt (ORCID: https://orcid.org/0000-0003-2926-343X)
- Peggi M. Angel (ORCID: https://orcid.org/0000-0002-4436-555X)
- Richard R. Drake (ORCID: https://orcid.org/0000-0002-6285-6440)
- Jordan P. Hartig (ORCID: https://orcid.org/0009-0000-2569-3585)
- Robin J. Leach (ORCID: https://orcid.org/0000-0002-3201-5579)
- Hani Nakhoul (ORCID: https://orcid.org/0000-0002-8045-2175)
- Deyali Chatterjee (ORCID: https://orcid.org/0000-0002-3322-1163)
- Jennifer K. Sehn (ORCID: https://orcid.org/0000-0002-7858-7425)
- Grace Grimsley
- Eric H. Kim (ORCID: https://orcid.org/0000-0002-0284-8342)
- Jennifer D. Wu (ORCID: https://orcid.org/0000-0002-8925-268X)
- Elena Núñez (ORCID: https://orcid.org/0000-0003-4911-8176)
Institutions
- Northwestern University (US)
- University of Nevada, Reno (US)
- Medical University of South Carolina (US)
- Eastern Virginia Medical School (US)
- The University of Texas at San Antonio Health Science Center (US)
- University of Washington (US)
- Washington University in St. Louis (US)
- The University of Texas at San Antonio (US)
- Saint Louis University (US)
- Vanderbilt University Medical Center (US)
Publication Details
- Journal
- Molecular Cancer Research
- Published
- 2024-10-17
- DOI
- https://doi.org/10.1158/1541-7786.mcr-24-0660
- Citations
- 4
- Primary Topic
- Mass Spectrometry Techniques and Applications
- Type
- article
- Field-Weighted Citation Impact
- 0.96
Funders
- U.S. Department of Defense
- American Cancer Society
- Prostate Cancer Foundation
- Foundation for Barnes-Jewish Hospital
- Alvin J. Siteman Cancer Center
- National Cancer Institute