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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7824149 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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