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Open AccessArticle

TGFBI Protein Is Increased in the Urine of Patients with High-Grade Urothelial Carcinomas, and Promotes Cell Proliferation and Migration

1
Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum (IPA), Bürkle-de-la-Camp Platz 1, 44789 Bochum, Germany
2
Department of Urology, Marien Hospital Herne, University Hospital of the Ruhr University Bochum, Hölkeskampring 40, 44625 Herne, Germany
3
Institute of Pathology, Georgius Agricola Stiftung Ruhr, Ruhr University Bochum, Bürkle-de-la-Camp Platz 1, 44789 Bochum, Germany
*
Author to whom correspondence should be addressed.
Current address: Institute of Pharmacology and Toxicology, RWTH Aachen University, 52074 Aachen, Germany.
Current address: Institute of Epidemiology and Social Medicine, University of Münster, 48149 Münster, Germany.
§
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(18), 4483; https://doi.org/10.3390/ijms20184483
Received: 2 August 2019 / Revised: 5 September 2019 / Accepted: 6 September 2019 / Published: 11 September 2019
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Here, we discovered TGFBI as a new urinary biomarker for muscle invasive and high-grade urothelial carcinoma (UC). After biomarker identification using antibody arrays, results were verified in urine samples from a study population consisting of 303 patients with UC, and 128 urological and 58 population controls. The analyses of possible modifying factors (age, sex, smoking status, urinary leukocytes and erythrocytes, and history of UC) were calculated by multiple logistic regression. Additionally, we performed knockdown experiments with TGFBI siRNA in bladder cancer cells and investigated the effects on proliferation and migration by wound closure assays and BrdU cell cycle analysis. TGFBI concentrations in urine are generally increased in patients with UC when compared to urological and population controls (1321.0 versus 701.3 and 475.6 pg/mg creatinine, respectively). However, significantly increased TGFBI was predominantly found in muscle invasive (14,411.7 pg/mg creatinine), high-grade (8190.7 pg/mg) and de novo UC (1856.7 pg/mg; all p < 0.0001). Knockdown experiments in vitro led to a significant decline of cell proliferation and migration. In summary, our results suggest a critical role of TGFBI in UC tumorigenesis and particularly in high-risk UC patients with poor prognosis and an elevated risk of progression on the molecular level. View Full-Text
Keywords: urothelial carcinoma; transforming growth factor beta-induced protein; TGFBI; βIGH3; proliferation; migration urothelial carcinoma; transforming growth factor beta-induced protein; TGFBI; βIGH3; proliferation; migration
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Lang, K.; Kahveci, S.; Bonberg, N.; Wichert, K.; Behrens, T.; Hovanec, J.; Roghmann, F.; Noldus, J.; Tam, Y.C.; Tannapfel, A.; Käfferlein, H.U.; Brüning, T. TGFBI Protein Is Increased in the Urine of Patients with High-Grade Urothelial Carcinomas, and Promotes Cell Proliferation and Migration. Int. J. Mol. Sci. 2019, 20, 4483.

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