TY - JOUR

T1 - Circulating Forms of Urokinase-Type Plasminogen Activator Receptor in Plasma Can Predict Recurrence and Survival in Patients with Urothelial Carcinoma of the Bladder

AU - Dohn, Line H

AU - Thind, Peter

AU - Salling, Lisbeth

AU - Lindberg, Henriette

AU - Oersted, Sofie

AU - Christensen, Ib J

AU - Laerum, Ole D

AU - Illemann, Martin

AU - von der Maase, Hans

AU - Høyer-Hansen, Gunilla

AU - Pappot, Helle

N1 - Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/5/14

Y1 - 2021/5/14

N2 - 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.

AB - 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.

KW - Biomarker

KW - Bladder cancer

KW - Blood

KW - Plasma

KW - Plasminogen activation

KW - Recurrence

KW - Survival

KW - UPAR

KW - Urokinase receptor

KW - Urothelial cancer

UR - http://www.scopus.com/inward/record.url?scp=85105710770&partnerID=8YFLogxK

U2 - 10.3390/cancers13102377

DO - 10.3390/cancers13102377

M3 - Journal article

C2 - 34069121

VL - 13

JO - Cancers

JF - Cancers

SN - 2072-6694

IS - 10

M1 - 2377

ER -