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

M Grunnet, I J Christensen, U Lassen, L H Jensen, M Lydolph, I K Lund, T Thurison, G Høyer-Hansen, M Mau-Sørensen

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Abstrakt

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.

OriginalsprogEngelsk
TidsskriftClinical Biochemistry
Vol/bind47
Udgave nummer7-8
Sider (fra-til)599-604
ISSN0009-9120
DOI
StatusUdgivet - maj 2014

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