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Clinical validation of chemotherapy predictors developed on global microRNA expression in the NCI60 cell line panel tested in ovarian cancer

OBJECTIVE: Ovarian cancer is the leading cause of death among gynecologic malignancies. This is partly due to a non-durable response to chemotherapy. Prediction of resistance to chemotherapy could be a key role in more personalized treatment. In the current study we aimed to examine if microRNA base...

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Autores principales: Prahm, Kira Philipsen, Høgdall, Claus, Karlsen, Mona Aarenstrup, Christensen, Ib Jarle, Novotny, Guy Wayne, Knudsen, Steen, Hansen, Anker, Jensen, Peter Buhl, Jensen, Thomas, Mirza, Mansoor Raza, Ekmann-Gade, Anne Weng, Nedergaard, Lotte, Høgdall, Estrid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363866/
https://www.ncbi.nlm.nih.gov/pubmed/28334047
http://dx.doi.org/10.1371/journal.pone.0174300
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author Prahm, Kira Philipsen
Høgdall, Claus
Karlsen, Mona Aarenstrup
Christensen, Ib Jarle
Novotny, Guy Wayne
Knudsen, Steen
Hansen, Anker
Jensen, Peter Buhl
Jensen, Thomas
Mirza, Mansoor Raza
Ekmann-Gade, Anne Weng
Nedergaard, Lotte
Høgdall, Estrid
author_facet Prahm, Kira Philipsen
Høgdall, Claus
Karlsen, Mona Aarenstrup
Christensen, Ib Jarle
Novotny, Guy Wayne
Knudsen, Steen
Hansen, Anker
Jensen, Peter Buhl
Jensen, Thomas
Mirza, Mansoor Raza
Ekmann-Gade, Anne Weng
Nedergaard, Lotte
Høgdall, Estrid
author_sort Prahm, Kira Philipsen
collection PubMed
description OBJECTIVE: Ovarian cancer is the leading cause of death among gynecologic malignancies. This is partly due to a non-durable response to chemotherapy. Prediction of resistance to chemotherapy could be a key role in more personalized treatment. In the current study we aimed to examine if microRNA based predictors could predict resistance to chemotherapy in ovarian cancer, and to investigate if the predictors could be prognostic factors for progression free and overall survival. METHODS: Predictors of chemotherapy-resistance were developed based on correlation between miRNA expression and differences in measured growth inhibition in a variety of human cancer cell lines in the presence of Carboplatin, Paclitaxel and Docetaxel. These predictors were then, retrospectively, blindly validated in a cohort of 170 epithelial ovarian cancer patients treated with Carboplatin and Paclitaxel or Docetaxel as first line treatment. RESULTS: In a multivariate cox proportional analysis the predictors of chemotherapy-resistance were not able to predict time to progression after end of chemotherapy (hazard ratio: 0.64, 95% CI: 0.36–1.12, P = 0.117). However, in a multivariate logistic analysis, where time to progression was considered as either more or less than 6 months, the predictors match clinical observed chemotherapy-resistance (odds ratio: 0.19, 95% CI: 0.05–0.73, P = 0.015). Neither univariate nor multivariate, time-dependent, cox analysis for progression free survival (PFS) or overall survival (OS) in all 170 patients showed to match predicted resistance to chemotherapy (PFS: hazard ratio: 0.69, 95% CI: 0.40–1.19, P = 0.183, OS: hazard ratio: 0.76, 95% CI: 0.42–1.40, P = 0.386). CONCLUSION: In the current study, microRNA based predictors of chemotherapy-resistance did not demonstrate any convincing correlation to clinical observed chemotherapy-resistance, progression free survival, or overall survival, in patients with epithelial ovarian cancer. However the predictors did reflect relapse more or less than 6 months.
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spelling pubmed-53638662017-04-06 Clinical validation of chemotherapy predictors developed on global microRNA expression in the NCI60 cell line panel tested in ovarian cancer Prahm, Kira Philipsen Høgdall, Claus Karlsen, Mona Aarenstrup Christensen, Ib Jarle Novotny, Guy Wayne Knudsen, Steen Hansen, Anker Jensen, Peter Buhl Jensen, Thomas Mirza, Mansoor Raza Ekmann-Gade, Anne Weng Nedergaard, Lotte Høgdall, Estrid PLoS One Research Article OBJECTIVE: Ovarian cancer is the leading cause of death among gynecologic malignancies. This is partly due to a non-durable response to chemotherapy. Prediction of resistance to chemotherapy could be a key role in more personalized treatment. In the current study we aimed to examine if microRNA based predictors could predict resistance to chemotherapy in ovarian cancer, and to investigate if the predictors could be prognostic factors for progression free and overall survival. METHODS: Predictors of chemotherapy-resistance were developed based on correlation between miRNA expression and differences in measured growth inhibition in a variety of human cancer cell lines in the presence of Carboplatin, Paclitaxel and Docetaxel. These predictors were then, retrospectively, blindly validated in a cohort of 170 epithelial ovarian cancer patients treated with Carboplatin and Paclitaxel or Docetaxel as first line treatment. RESULTS: In a multivariate cox proportional analysis the predictors of chemotherapy-resistance were not able to predict time to progression after end of chemotherapy (hazard ratio: 0.64, 95% CI: 0.36–1.12, P = 0.117). However, in a multivariate logistic analysis, where time to progression was considered as either more or less than 6 months, the predictors match clinical observed chemotherapy-resistance (odds ratio: 0.19, 95% CI: 0.05–0.73, P = 0.015). Neither univariate nor multivariate, time-dependent, cox analysis for progression free survival (PFS) or overall survival (OS) in all 170 patients showed to match predicted resistance to chemotherapy (PFS: hazard ratio: 0.69, 95% CI: 0.40–1.19, P = 0.183, OS: hazard ratio: 0.76, 95% CI: 0.42–1.40, P = 0.386). CONCLUSION: In the current study, microRNA based predictors of chemotherapy-resistance did not demonstrate any convincing correlation to clinical observed chemotherapy-resistance, progression free survival, or overall survival, in patients with epithelial ovarian cancer. However the predictors did reflect relapse more or less than 6 months. Public Library of Science 2017-03-23 /pmc/articles/PMC5363866/ /pubmed/28334047 http://dx.doi.org/10.1371/journal.pone.0174300 Text en © 2017 Prahm et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Prahm, Kira Philipsen
Høgdall, Claus
Karlsen, Mona Aarenstrup
Christensen, Ib Jarle
Novotny, Guy Wayne
Knudsen, Steen
Hansen, Anker
Jensen, Peter Buhl
Jensen, Thomas
Mirza, Mansoor Raza
Ekmann-Gade, Anne Weng
Nedergaard, Lotte
Høgdall, Estrid
Clinical validation of chemotherapy predictors developed on global microRNA expression in the NCI60 cell line panel tested in ovarian cancer
title Clinical validation of chemotherapy predictors developed on global microRNA expression in the NCI60 cell line panel tested in ovarian cancer
title_full Clinical validation of chemotherapy predictors developed on global microRNA expression in the NCI60 cell line panel tested in ovarian cancer
title_fullStr Clinical validation of chemotherapy predictors developed on global microRNA expression in the NCI60 cell line panel tested in ovarian cancer
title_full_unstemmed Clinical validation of chemotherapy predictors developed on global microRNA expression in the NCI60 cell line panel tested in ovarian cancer
title_short Clinical validation of chemotherapy predictors developed on global microRNA expression in the NCI60 cell line panel tested in ovarian cancer
title_sort clinical validation of chemotherapy predictors developed on global microrna expression in the nci60 cell line panel tested in ovarian cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363866/
https://www.ncbi.nlm.nih.gov/pubmed/28334047
http://dx.doi.org/10.1371/journal.pone.0174300
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