title: Release of urinary extracellular vesicles in prostate cancer is associated with altered urinary N-glycosylation profile.
abstract: OBJECTIVE
  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 ofn-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.
authors.affiliation: Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Tijl
authors.initials: T
authors.lastname: Vermassen
authors.affiliation: Department of Basic Medical Sciences, Ghent University, Ghent, Belgium.
authors.forename: Katharina
authors.initials: K
authors.lastname: D'Herde
authors.affiliation: Department of Basic Medical Sciences, Ghent University, Ghent, Belgium.
authors.forename: Dominique
authors.initials: D
authors.lastname: Jacobus
authors.affiliation: Department of Urology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Charles
authors.initials: C
authors.lastname: Van Praet
authors.affiliation: Department of Urology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Filip
authors.initials: F
authors.lastname: Poelaert
authors.affiliation: Department of Urology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Nicolaas
authors.initials: N
authors.lastname: Lumen
authors.affiliation: Unit for Medical Biotechnology, Inflammation Research Center, VIB-Ghent University, Ghent, Belgium.
authors.forename: Nico
authors.initials: N
authors.lastname: Callewaert
authors.affiliation: Department of Urology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Karel
authors.initials: K
authors.lastname: Decaestecker
authors.affiliation: Department of Radiology and Nuclear Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Villeirs
authors.affiliation: Department of Urology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Piet
authors.initials: P
authors.lastname: Hoebeke
authors.affiliation: Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Simon
authors.initials: S
authors.lastname: Van Belle
authors.affiliation: Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rottey
authors.affiliation: Department of Clinical Chemistry, Ghent University Hospital, Ghent, Belgium.
authors.forename: Joris
authors.initials: J
authors.lastname: Delanghe
mesh_terms: D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000652:urine*; D000067128:Extracellular Vesicles / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000652:urine*; D011471:Prostatic Neoplasms / Q000652:urine*; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen
keywords: CHEMICAL PATHOLOGY; DIAGNOSIS; PROSTATE; PROTEINS