The prognostic relevance of urokinase-type plasminogen activator (uPA) in the blood of patients with metastatic breast cancer

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Details zur Publikation

Autor(en): Banys-Paluchowski M, Witzel I, Aktas B, Fasching P, Hartkopf A, Janni W, Kasimir-Bauer S, Pantel K, Schoen G, Rack B, Riethdorf S, Solomayer EF, Fehm T, Mueller V
Zeitschrift: Scientific Reports
Jahr der Veröffentlichung: 2019
Band: 9
ISSN: 2045-2322


Abstract

In breast cancer (BC), elevated levels of urokinase-type plasminogen activator (uPA) in tumor tissue have been confirmed as a strong prognostic factor in level-of-evidence-1 studies. The aim of the present study was to evaluate the clinical relevance of uPA levels in serum of metastatic BC patients and to compare uPA with other blood-based biomarkers. 252 patients were enrolled in this prospective, multicentre study. Blood samples were collected before begin of first-line or later-line systemic treatment. Serum uPA was quantified by a commercially available ELISA. Circulating tumor cells (CTCs) were detected using CellSearch; other biomarkers (EGFR, VEGF, HER2, RAS p21, TIMP1, CAIX) by ELISA. Using the ROC analysis, the optimal cut-off value (determined by the Youden index) of serum uPA was 2.52 ng/ml. Using this value, 26% of patients had elevated uPA levels. Patients with visceral metastasis and more than one metastatic site were significantly more likely to present with elevated uPA levels. CTC status, serum HER2, RAS p21, CAIX, TIMP1 and VEGF correlated significantly with uPA levels. Elevated uPA levels predicted shorter overall and progression-free survival in univariate analysis (median OS: 7.5 months [95%-CI 4.5-10.5 months] vs. not reached, p < 0.001; PFS:4.8 [95%CI: 3.1-6.5] vs. 9.1 [7.4-10.8] months, p < 0.001). In multivariate analysis, elevated uPA, presence of >= 5 CTCs, elevated RAS p21, higher grading and higher line of therapy were independent predictors of shorter OS, while elevated CTC counts, higher line of therapy and negative estrogen receptor status were independent predictors of shorter PFS. In conclusion, elevated uPA levels independently predict reduced overall survival and improved prognostication in patients with known CTC status. Whether high serum uPA might identify patients most likely to benefit from therapies targeting uPA, remains to be evaluated in future trials.


FAU-Autoren / FAU-Herausgeber

Fasching, Peter PD Dr.
Professur für Translationale Frauenheilkunde und Geburtshilfe


Autor(en) der externen Einrichtung(en)
Asklepios Klinik Altona
Eberhard Karls Universität Tübingen
Heinrich-Heine-Universität Düsseldorf
Universität Duisburg-Essen (UDE)
Universitätsklinikum des Saarlandes
Universitätsklinikum Hamburg-Eppendorf (UKE)
Universitätsklinikum Leipzig
Universitätsklinikum Ulm


Zitierweisen

APA:
Banys-Paluchowski, M., Witzel, I., Aktas, B., Fasching, P., Hartkopf, A., Janni, W.,... Mueller, V. (2019). The prognostic relevance of urokinase-type plasminogen activator (uPA) in the blood of patients with metastatic breast cancer. Scientific Reports, 9. https://dx.doi.org/10.1038/s41598-018-37259-2

MLA:
Banys-Paluchowski, Malgorzata, et al. "The prognostic relevance of urokinase-type plasminogen activator (uPA) in the blood of patients with metastatic breast cancer." Scientific Reports 9 (2019).

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Zuletzt aktualisiert 2019-08-03 um 00:08