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MMP-7 Serum and Tissue Levels Are Associated with Poor Survival in Platinum-Treated Bladder Cancer Patients

Chemotherapy resistance is a main cause of therapeutic failure and death in bladder cancer. With the approval of immune checkpoint inhibitors, prediction of platinum treatment became of great clinical importance. Matrix metalloproteinase-7 (MMP-7) was shown to be involved in cisplatin resistance. Th...

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Autores principales: Szarvas, Tibor, Hoffmann, Michèle J., Olah, Csilla, Szekely, Eszter, Kiss, Andras, Hess, Jochen, Tschirdewahn, Stephan, Hadaschik, Boris, Grotheer, Vera, Nyirady, Peter, Csizmarik, Anita, Varadi, Melinda, Reis, Henning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824149/
https://www.ncbi.nlm.nih.gov/pubmed/33396213
http://dx.doi.org/10.3390/diagnostics11010048
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author Szarvas, Tibor
Hoffmann, Michèle J.
Olah, Csilla
Szekely, Eszter
Kiss, Andras
Hess, Jochen
Tschirdewahn, Stephan
Hadaschik, Boris
Grotheer, Vera
Nyirady, Peter
Csizmarik, Anita
Varadi, Melinda
Reis, Henning
author_facet Szarvas, Tibor
Hoffmann, Michèle J.
Olah, Csilla
Szekely, Eszter
Kiss, Andras
Hess, Jochen
Tschirdewahn, Stephan
Hadaschik, Boris
Grotheer, Vera
Nyirady, Peter
Csizmarik, Anita
Varadi, Melinda
Reis, Henning
author_sort Szarvas, Tibor
collection PubMed
description Chemotherapy resistance is a main cause of therapeutic failure and death in bladder cancer. With the approval of immune checkpoint inhibitors, prediction of platinum treatment became of great clinical importance. Matrix metalloproteinase-7 (MMP-7) was shown to be involved in cisplatin resistance. Therefore, tissue and circulating MMP-7 levels were evaluated in 124 bladder cancer patients who received postoperative platinum-based chemotherapy. Tissue MMP-7 levels were analyzed by immunohistochemistry in 72 formalin-fixed, paraffin-embedded chemo-naïve tumor samples, while MMP-7 serum concentrations were determined in 132 serum samples of an independent cohort of 52 patients. MMP-7 tissue and serum levels were correlated with clinicopathological and follow-up data. MMP-7 gene expression was determined by RT-qPCR in 20 urothelial cancer cell lines and two non-malignant urothelial cell lines. MMP-7 was overexpressed in RT-112 and T-24 cells by stable transfection, to assess its functional involvement in platinum sensitivity. High MMP-7 tissue expression and pretreatment serum concentrations were independently associated with poor overall survival (tissue HR = 2.296, 95%CI = 1.235–4.268 and p = 0.009; serum HR = 2.743, 95%CI = 1.258–5.984 and p = 0.011). Therefore, MMP-7 tissue and serum analysis may help to optimize therapeutic decisions. Stable overexpression in RT-112 and T-24 cells did not affect platinum sensitivity.
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spelling pubmed-78241492021-01-24 MMP-7 Serum and Tissue Levels Are Associated with Poor Survival in Platinum-Treated Bladder Cancer Patients Szarvas, Tibor Hoffmann, Michèle J. Olah, Csilla Szekely, Eszter Kiss, Andras Hess, Jochen Tschirdewahn, Stephan Hadaschik, Boris Grotheer, Vera Nyirady, Peter Csizmarik, Anita Varadi, Melinda Reis, Henning Diagnostics (Basel) Article Chemotherapy resistance is a main cause of therapeutic failure and death in bladder cancer. With the approval of immune checkpoint inhibitors, prediction of platinum treatment became of great clinical importance. Matrix metalloproteinase-7 (MMP-7) was shown to be involved in cisplatin resistance. Therefore, tissue and circulating MMP-7 levels were evaluated in 124 bladder cancer patients who received postoperative platinum-based chemotherapy. Tissue MMP-7 levels were analyzed by immunohistochemistry in 72 formalin-fixed, paraffin-embedded chemo-naïve tumor samples, while MMP-7 serum concentrations were determined in 132 serum samples of an independent cohort of 52 patients. MMP-7 tissue and serum levels were correlated with clinicopathological and follow-up data. MMP-7 gene expression was determined by RT-qPCR in 20 urothelial cancer cell lines and two non-malignant urothelial cell lines. MMP-7 was overexpressed in RT-112 and T-24 cells by stable transfection, to assess its functional involvement in platinum sensitivity. High MMP-7 tissue expression and pretreatment serum concentrations were independently associated with poor overall survival (tissue HR = 2.296, 95%CI = 1.235–4.268 and p = 0.009; serum HR = 2.743, 95%CI = 1.258–5.984 and p = 0.011). Therefore, MMP-7 tissue and serum analysis may help to optimize therapeutic decisions. Stable overexpression in RT-112 and T-24 cells did not affect platinum sensitivity. MDPI 2020-12-31 /pmc/articles/PMC7824149/ /pubmed/33396213 http://dx.doi.org/10.3390/diagnostics11010048 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Szarvas, Tibor
Hoffmann, Michèle J.
Olah, Csilla
Szekely, Eszter
Kiss, Andras
Hess, Jochen
Tschirdewahn, Stephan
Hadaschik, Boris
Grotheer, Vera
Nyirady, Peter
Csizmarik, Anita
Varadi, Melinda
Reis, Henning
MMP-7 Serum and Tissue Levels Are Associated with Poor Survival in Platinum-Treated Bladder Cancer Patients
title MMP-7 Serum and Tissue Levels Are Associated with Poor Survival in Platinum-Treated Bladder Cancer Patients
title_full MMP-7 Serum and Tissue Levels Are Associated with Poor Survival in Platinum-Treated Bladder Cancer Patients
title_fullStr MMP-7 Serum and Tissue Levels Are Associated with Poor Survival in Platinum-Treated Bladder Cancer Patients
title_full_unstemmed MMP-7 Serum and Tissue Levels Are Associated with Poor Survival in Platinum-Treated Bladder Cancer Patients
title_short MMP-7 Serum and Tissue Levels Are Associated with Poor Survival in Platinum-Treated Bladder Cancer Patients
title_sort mmp-7 serum and tissue levels are associated with poor survival in platinum-treated bladder cancer patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824149/
https://www.ncbi.nlm.nih.gov/pubmed/33396213
http://dx.doi.org/10.3390/diagnostics11010048
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