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J Clin Pathol. 2017 Oct;70(10):838-846. doi: 10.1136/jclinpath-2016-204312. Epub 2017 Mar 30.

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

Author information

1
Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium.
2
Department of Basic Medical Sciences, Ghent University, Ghent, Belgium.
3
Department of Urology, Ghent University Hospital, Ghent, Belgium.
4
Unit for Medical Biotechnology, Inflammation Research Center, VIB-Ghent University, Ghent, Belgium.
5
Department of Radiology and Nuclear Medicine, Ghent University Hospital, Ghent, Belgium.
6
Department of Clinical Chemistry, Ghent University Hospital, Ghent, Belgium.

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:

CHEMICAL PATHOLOGY; DIAGNOSIS; PROSTATE; PROTEINS

PMID:
28360190
DOI:
10.1136/jclinpath-2016-204312
[Indexed for MEDLINE]

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