ArticleScientific reports2019
The prognostic relevance of urokinase-type plasminogen activator (uPA) in the blood of patients with metastatic breast cancer.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- Differentiating borderline HER2-expressing and HER2-positive cancers from other subtypes using serum urokinase plasminogen activator.British journal of cancer · 2026Article
- Emerging roles of haemostatic proteins as markers of disease progression and prognosis in breast cancer.Exploration of targeted anti-tumor therapy · 2026Review
- ERK3/MAPK6 promotes triple-negative breast cancer progression through collective migration and EMT plasticity.Frontiers in oncology · 2025Article
- Phase I Trial of Upamostat Combined With Gemcitabine in Locally Unresectable or Metastatic Pancreatic Cancer: Safety and Preliminary Efficacy Assessment.Cancer medicine · 2025Article
- ALDH1A3 promotes invasion and metastasis in triple-negative breast cancer by regulating the plasminogen activation pathway.Molecular oncology · 2024Article
- The Enigma of Mammaglobin: Redefining the Biomarker Paradigm in Breast Carcinoma.International journal of molecular sciences · 2023Review
- Functional Validation of the Putative Oncogenic Activity ofBiomedicines · 2022Article
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- Inhaled Gold Nano-star Carriers for Targeted Delivery of Triple Suicide Gene Therapy and Therapeutic MicroRNAs to Lung Metastases: Development and Validation in a Small Animal Model.Advanced therapeutics · 2022Article
- Identification of prognostic genes in the pancreatic adenocarcinoma immune microenvironment by integrated bioinformatics analysis.Cancer immunology, immunotherapy : CII · 2022Article
- Identification of key tumor stroma-associated transcriptional signatures correlated with survival prognosis and tumor progression in breast cancer.Breast cancer (Tokyo, Japan) · 2022Article
- Urokinase plasminogen activator as an anti-metastasis target: inhibitor design principles, recent amiloride derivatives, and issues with human/mouse species selectivity.Biophysical reviews · 2022Review
- Review
- Metastatic phenotype and immunosuppressive tumour microenvironment in pancreatic ductal adenocarcinoma: Key role of the urokinase plasminogen activator (PLAU).Frontiers in immunology · 2022Article
- Global Increase in Breast Cancer Incidence: Risk Factors and Preventive Measures.BioMed research international · 2022Review
- The Plasminogen-Activator Plasmin System in Physiological and Pathophysiological Angiogenesis.International journal of molecular sciences · 2021Review
- One-pot synthesis of α-aminophosphonates by yttrium-catalyzed Birum-Oleksyszyn reaction.RSC advances · 2021Article
- Review
- Article
- Overexpression of PSMC2 promotes the tumorigenesis and development of human breast cancer via regulating plasminogen activator urokinase (PLAU).Cell death & disease · 2021Article
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Authors and funding
14 authors at 9 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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