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

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 (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 9

DOI: 10.1038/s41598-018-37259-2

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.

Authors with CRIS profile

Peter Fasching Professur für Translationale Frauenheilkunde und Geburtshilfe

Involved external institutions

Asklepios Klinik Altona DE Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) Universitätsklinikum Leipzig DE Germany (DE) Eberhard Karls Universität Tübingen DE Germany (DE) Universitätsklinikum Ulm DE Germany (DE) Universität Duisburg-Essen (UDE) DE Germany (DE) Universitätsklinikum des Saarlandes (UKS) DE Germany (DE) Heinrich-Heine-Universität Düsseldorf DE Germany (DE)

How to cite

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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