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Circulating Forms of Urokinase-Type Plasminogen Activator Receptor in Plasma Can Predict Recurrence and Survival in Patients with Urothelial Carcinoma of the Bladder

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Urothelial carcinoma of the bladder is a highly aggressive disease characterised by a very heterogeneous clinical outcome. Despite cystectomy, patients still have a high recurrence risk and shortened survival. Urokinase-type plasminogen activator receptor (uPAR) is present in tumour tissue specimens from patients with urothelial carcinoma. The different uPAR forms in blood are strong prognostic markers in other cancer types. We investigate the presence of different uPAR forms in tumour tissue and test the hypothesis that preoperative plasma levels of the uPAR forms predict recurrence free survival, cancer specific survival, and overall survival in patients treated with cystectomy for urothelial carcinoma. Using Western blotting we analyse neoplasia and adjacent benign-appearing urothelium from randomly selected patients for the presence of intact and cleaved uPAR forms. Prospectively collected preoperative plasma samples from 107 patients who underwent radical cystectomy for urothelial carcinoma are analysed. The different uPAR forms are measured by time-resolved fluorescence immunoassays. uPAR in tumour tissue from patients with urothelial carcinoma is demonstrated in both an intact and cleaved form. The different uPAR forms in plasma are all significantly associated with both recurrence free survival, cancer specific survival, and overall survival, high concentrations predicting short survival. uPAR (I) has the strongest association with a HR of 2.56 for overall survival. In the multivariable survival analysis uPAR (I) is significantly associated with cancer specific survival and overall survival.

OriginalsprogEngelsk
Artikelnummer2377
TidsskriftCancers
Vol/bind13
Udgave nummer10
ISSN2072-6694
DOI
StatusUdgivet - 14 maj 2021

Bibliografisk note

Funding Information:
Funding: This research was supported by The Oncological Research Foundation at the Department of Oncology at Rigshospitalet, Danish Cancer Research Foundation, Merchant Georg Bjørkner and wife Ellen Bjørkner Foundation, and The Harboe Foundation. Line Hammer Dohn received each award. Grant numbers and URL of websites are not available. None of the funders played any role in the study design, data collection and analysis, decision to publish, or preparation for the manuscript.

ID: 65946169