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Release of urinary extracellular vesicles in prostate cancer is associated with altered urinary N-glycosylation profile

Tijl Vermassen (UGent) , Katharina D'Herde (UGent) , Dominique Jacobus (UGent) , Charles Van Praet (UGent) , Filip Poelaert (UGent) , Nicolaas Lumen (UGent) , Nico Callewaert (UGent) , Karel Decaestecker (UGent) , Geert Villeirs (UGent) , Piet Hoebeke (UGent) , et al.
(2017) JOURNAL OF CLINICAL PATHOLOGY. 70(10). p.838-846
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Abstract
Aim: Nowadays, extracellular vesicles are of great interest in prostate cancer (PCa) research. Asparagine (N)-linked glycosylation could play a significant role in the pathological mechanism of these vesicles. We investigated if prostatic protein N-glycosylation profiles were related to urinary vesicle-associated prostate-specific antigen (PSA) extractability and if this parameter showed diagnostic potential for PCa. Methods: Urinary extracellular vesicles were visualised using transmission electron microscopy. Urinary extracellular vesicles extraction by means of n-butanol allowed determination of urinary vesicle-associated PSA extractability. Diagnostic value was assessed between benign prostate hyperplasia (BPH; n=122) and patients with PCa (n=85). Additionally, correlation with urine N-glycosylation was assessed. Results: Urinary extracellular vesicles with a diameter of approximately 100 nm were more abundantly present in urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001). Next, vesicle-associated PSA extraction ratio was correlated to biantennary core-fucosylation (p=0.003). Finally, vesicle-associated PSA extraction ratio proved beneficial in PCa diagnosis, next to serum PSA and the urinary glycosylation marker (p=0.021). Conclusions: The urinary vesicle-associated PSA extraction ratio is increased in PCa which is a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa. The urinary vesicle-associated PSA extraction ratio was associated with changes in N-glycoforms and showed diagnostic potential. Further research is warranted to unravel the pathological link between N-glycosylation and extracellular vesicles in cancer, as well as to assess the prognostic value of this biomarker.
Keywords
ALKALINE-PHOSPHATASE, EXOSOMES, ANTIGEN, SERUM, EXTRACTION, CARCINOMA, BIOMARKER, CELLS, LYSOPHOSPHOLIPIDS, MICROVESICLES

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Chicago
Vermassen, Tijl, Katharina D’Herde, Dominique Jacobus, Charles Van Praet, Filip Poelaert, Nicolaas Lumen, Nico Callewaert, et al. 2017. “Release of Urinary Extracellular Vesicles in Prostate Cancer Is Associated with Altered Urinary N-glycosylation Profile.” Journal of Clinical Pathology 70 (10): 838–846.
APA
Vermassen, T., D’Herde, K., Jacobus, D., Van Praet, C., Poelaert, F., Lumen, N., Callewaert, N., et al. (2017). Release of urinary extracellular vesicles in prostate cancer is associated with altered urinary N-glycosylation profile. JOURNAL OF CLINICAL PATHOLOGY, 70(10), 838–846.
Vancouver
1.
Vermassen T, D’Herde K, Jacobus D, Van Praet C, Poelaert F, Lumen N, et al. Release of urinary extracellular vesicles in prostate cancer is associated with altered urinary N-glycosylation profile. JOURNAL OF CLINICAL PATHOLOGY. 2017;70(10):838–46.
MLA
Vermassen, Tijl, Katharina D’Herde, Dominique Jacobus, et al. “Release of Urinary Extracellular Vesicles in Prostate Cancer Is Associated with Altered Urinary N-glycosylation Profile.” JOURNAL OF CLINICAL PATHOLOGY 70.10 (2017): 838–846. Print.
@article{8517445,
  abstract     = {Aim: Nowadays, extracellular vesicles are of great interest in prostate cancer (PCa) research. Asparagine (N)-linked glycosylation could play a significant role in the pathological mechanism of these vesicles. We investigated if prostatic protein N-glycosylation profiles were related to urinary vesicle-associated prostate-specific antigen (PSA) extractability and if this parameter showed diagnostic potential for PCa. 
Methods: Urinary extracellular vesicles were visualised using transmission electron microscopy. Urinary extracellular vesicles extraction by means of n-butanol allowed determination of urinary vesicle-associated PSA extractability. Diagnostic value was assessed between benign prostate hyperplasia (BPH; n=122) and patients with PCa (n=85). Additionally, correlation with urine N-glycosylation was assessed. 
Results: Urinary extracellular vesicles with a diameter of approximately 100 nm were more abundantly present in urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p{\textlangle}0.001). Next, vesicle-associated PSA extraction ratio was correlated to biantennary core-fucosylation (p=0.003). Finally, vesicle-associated PSA extraction ratio proved beneficial in PCa diagnosis, next to serum PSA and the urinary glycosylation marker (p=0.021). 
Conclusions: The urinary vesicle-associated PSA extraction ratio is increased in PCa which is a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa. The urinary vesicle-associated PSA extraction ratio was associated with changes in N-glycoforms and showed diagnostic potential. Further research is warranted to unravel the pathological link between N-glycosylation and extracellular vesicles in cancer, as well as to assess the prognostic value of this biomarker.},
  author       = {Vermassen, Tijl and D'Herde, Katharina and Jacobus, Dominique and Van Praet, Charles and Poelaert, Filip and Lumen, Nicolaas and Callewaert, Nico and Decaestecker, Karel and Villeirs, Geert and Hoebeke, Piet and Van Belle, Simon and Rottey, Sylvie and Delanghe, Joris},
  issn         = {0021-9746},
  journal      = {JOURNAL OF CLINICAL PATHOLOGY},
  language     = {eng},
  number       = {10},
  pages        = {838--846},
  title        = {Release of urinary extracellular vesicles in prostate cancer is associated with altered urinary N-glycosylation profile},
  url          = {http://dx.doi.org/10.1136/jclinpath-2016-204312},
  volume       = {70},
  year         = {2017},
}

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