Prognostic significance of circulating intact and cleaved forms of urokinase plasminogen activator receptor in inoperable chemotherapy treated cholangiocarcinoma patients

TY - JOUR

T1 - Prognostic significance of circulating intact and cleaved forms of urokinase plasminogen activator receptor in inoperable chemotherapy treated cholangiocarcinoma patients

AU - Grunnet, Mie

AU - Christensen, I J

AU - Lassen, Ulrik

AU - Jensen, Lone Hummelshøj

AU - Lydolph, M

AU - Lund, I K

AU - Thurison, T

AU - Høyer-Hansen, G

AU - Mau-Sørensen, Morten

N1 - Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

PY - 2014/5

Y1 - 2014/5

N2 - Background: High levels of intact and cleaved forms of the urokinase-type plasminogen activator receptor (uPAR) in both tissue and blood are associated with poor survival in several cancer diseases. The prognostic significance of uPAR in cholangiocarcinoma is unknown. The aims of this study were to determine if pre-treatment serum levels of uPAR forms and a decrease in levels during chemotherapy are predictive of survival in patients with inoperable cholangiocarcinoma. Design and methods: Patients with inoperable cholangiocarcinoma were consecutively included in the training set (n = 108). A test set included patients from a different hospital using similar treatment guidelines (n = 60). Serum levels of the different uPAR forms were determined using time-resolved fluorescence immunoassays (TR-FIA). The Cox proportional hazards model was used for the uni- and multivariate survival analyses. Results: Baseline level of uPAR(I-III). +. uPAR(II-III) was an independent predictor of survival (HR = 2.08, 95% CI:1.46-2.97, p. <. 0.0001). Applying the linear predictor from the training set to the test set, it was validated that uPAR(I-III). +. uPAR(II-III) predicted overall survival (p = 0.049). A high level of uPAR(I-III). +. uPAR(II-III) after 2. cycles of chemotherapy was associated with poor survival (HR = 1.79, 95% CI:1.08-2.97, p = 0.023, n = 57). This predictor, however, was not significant in the test set (p = 0.21, 26 events in 27 patients). Conclusion: The baseline level of uPAR(I-III). +. uPAR(II-III) is a predictor of survival in inoperable cholangiocarcinoma patients.

AB - Background: High levels of intact and cleaved forms of the urokinase-type plasminogen activator receptor (uPAR) in both tissue and blood are associated with poor survival in several cancer diseases. The prognostic significance of uPAR in cholangiocarcinoma is unknown. The aims of this study were to determine if pre-treatment serum levels of uPAR forms and a decrease in levels during chemotherapy are predictive of survival in patients with inoperable cholangiocarcinoma. Design and methods: Patients with inoperable cholangiocarcinoma were consecutively included in the training set (n = 108). A test set included patients from a different hospital using similar treatment guidelines (n = 60). Serum levels of the different uPAR forms were determined using time-resolved fluorescence immunoassays (TR-FIA). The Cox proportional hazards model was used for the uni- and multivariate survival analyses. Results: Baseline level of uPAR(I-III). +. uPAR(II-III) was an independent predictor of survival (HR = 2.08, 95% CI:1.46-2.97, p. <. 0.0001). Applying the linear predictor from the training set to the test set, it was validated that uPAR(I-III). +. uPAR(II-III) predicted overall survival (p = 0.049). A high level of uPAR(I-III). +. uPAR(II-III) after 2. cycles of chemotherapy was associated with poor survival (HR = 1.79, 95% CI:1.08-2.97, p = 0.023, n = 57). This predictor, however, was not significant in the test set (p = 0.21, 26 events in 27 patients). Conclusion: The baseline level of uPAR(I-III). +. uPAR(II-III) is a predictor of survival in inoperable cholangiocarcinoma patients.

KW - Adult

KW - Aged

KW - Cholangiocarcinoma

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Prognosis

KW - Receptors, Urokinase Plasminogen Activator

KW - Retrospective Studies

KW - Tumor Markers, Biological

KW - Young Adult

U2 - 10.1016/j.clinbiochem.2014.01.030

DO - 10.1016/j.clinbiochem.2014.01.030

M3 - Journal article

C2 - 24530340

SN - 0009-9120

VL - 47

SP - 599

EP - 604

JO - Clinical Biochemistry

JF - Clinical Biochemistry

IS - 7-8

ER -