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.
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Handling editor Tahir Pillay
Contributors Study concept and design: TV, SVB, SR and JD. Patient enrolment: CVP, FP, NL, KD and PH. Data acquisition: TV and GV. Transmission electron microscopy: KDH and DJ. Carbohydrate electrophoresis: TV and NC. Data analysis and interpretation: TV, KDH, DJ and JD. Statistical analysis: TV. Manuscript preparation: TV. Manuscript editing: all authors. Manuscript review: all authors.
Funding Ghent University Hospital (Clinical Research Fund)
Competing interests None declared.
Ethics approval The study was approved by the local Ethics Committee of the Ghent University Hospital (Belgian registration number: B670201214356).
Provenance and peer review Not commissioned; externally peer reviewed.
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