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.

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©2024 The Authors; Published by the American Association for Cancer Research
2024
American Association for Cancer Research
This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license.
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Supplementary data

Supplementary Figure S1

Figure S1. Schematic of fucosylated glycan architecture.

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Supplementary Figure S2

Figure S2. Enrichment of glycans in specimens with small cell versus adenocarcinoma histology.

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Supplementary Figure S3

Figure S3. Ley expression in small cell prostate cancer.

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Supplementary Figure S4

Figure S4. Heat map of selected glycans of a GG5 adenocarcinoma.

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Supplementary Figure S5

Figure S5. Heat map of selected glycans of a metastatic small cell carcinoma to a lymph node.

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Supplementary Figure S6

Figure S6. Heat map of selected glycans of a mixed GG5 adenocarcinoma and small cell tumor.

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Supplementary Figure S7

Figure S7. Example of adenocarcinoma with NE features.

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Supplementary Figure S8

Figure S8. Fucosylated glycan expression in tumors from prostatectomy specimens do not associate with PSA, grade, or stage.

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Supplementary Table S1

Table S1. Patient data from the Washington University cohort.

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Supplementary Table S2

Table S2. Patient data from the University of Texas Health San Antonio Tissue Microarray.

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Supplementary Table S3

Table S3. List of Hyper-fucosylated glycans for prostate cancer analysis

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