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Tissue MicroRNAs as Predictors of Outcome in Patients with Metastatic Colorectal Cancer Treated with First Line Capecitabine and Oxaliplatin with or without Bevacizumab

PURPOSE: We tested the hypothesis that expression of microRNAs (miRNAs) in cancer tissue can predict effectiveness of bevacizumab added to capecitabine and oxaliplatin (CAPEOX) in patients with metastatic colorectal cancer (mCRC). EXPERIMENTAL DESIGN: Patients with mCRC treated with first line CAPEO...

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Autores principales: Boisen, Mogens K., Dehlendorff, Christian, Linnemann, Dorte, Nielsen, Boye S., Larsen, Jim S., Østerlind, Kell, Nielsen, Svend E., Tarpgaard, Line S., Qvortrup, Camilla, Pfeiffer, Per, Holländer, Niels H., Keldsen, Nina, Hansen, Torben F., Jensen, Brita B., Høgdall, Estrid V. S., Jensen, Benny V., Johansen, Julia S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4198118/
https://www.ncbi.nlm.nih.gov/pubmed/25329796
http://dx.doi.org/10.1371/journal.pone.0109430
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author Boisen, Mogens K.
Dehlendorff, Christian
Linnemann, Dorte
Nielsen, Boye S.
Larsen, Jim S.
Østerlind, Kell
Nielsen, Svend E.
Tarpgaard, Line S.
Qvortrup, Camilla
Pfeiffer, Per
Holländer, Niels H.
Keldsen, Nina
Hansen, Torben F.
Jensen, Brita B.
Høgdall, Estrid V. S.
Jensen, Benny V.
Johansen, Julia S.
author_facet Boisen, Mogens K.
Dehlendorff, Christian
Linnemann, Dorte
Nielsen, Boye S.
Larsen, Jim S.
Østerlind, Kell
Nielsen, Svend E.
Tarpgaard, Line S.
Qvortrup, Camilla
Pfeiffer, Per
Holländer, Niels H.
Keldsen, Nina
Hansen, Torben F.
Jensen, Brita B.
Høgdall, Estrid V. S.
Jensen, Benny V.
Johansen, Julia S.
author_sort Boisen, Mogens K.
collection PubMed
description PURPOSE: We tested the hypothesis that expression of microRNAs (miRNAs) in cancer tissue can predict effectiveness of bevacizumab added to capecitabine and oxaliplatin (CAPEOX) in patients with metastatic colorectal cancer (mCRC). EXPERIMENTAL DESIGN: Patients with mCRC treated with first line CAPEOX and bevacizumab (CAPEOXBEV): screening (n = 212) and validation (n = 121) cohorts, or CAPEOX alone: control cohort (n = 127), were identified retrospectively and archival primary tumor samples were collected. Expression of 754 miRNAs was analyzed in the screening cohort using polymerase chain reaction (PCR) arrays and expression levels were related to time to disease progression (TTP) and overall survival (OS). Significant miRNAs from the screening study were analyzed in all three cohorts using custom PCR arrays. In situ hybridization (ISH) was done for selected miRNAs. RESULTS: In the screening study, 26 miRNAs were significantly correlated with outcome in multivariate analyses. Twenty-two miRNAs were selected for further study. Higher miR-664-3p expression and lower miR-455-5p expression were predictive of improved outcome in the CAPEOXBEV cohorts and showed a significant interaction with bevacizumab effectiveness. The effects were strongest for OS. Both miRNAs showed high expression in stromal cells. Higher expression of miR-196b-5p and miR-592 predicted improved outcome regardless of bevacizumab treatment, with similar effect estimates in all three cohorts. CONCLUSIONS: We have identified potentially predictive miRNAs for bevacizumab effectiveness and additional miRNAs that could be related to chemotherapy effectiveness or prognosis in patients with mCRC. Our findings need further validation in large cohorts, preferably from completed randomized trials.
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spelling pubmed-41981182014-10-21 Tissue MicroRNAs as Predictors of Outcome in Patients with Metastatic Colorectal Cancer Treated with First Line Capecitabine and Oxaliplatin with or without Bevacizumab Boisen, Mogens K. Dehlendorff, Christian Linnemann, Dorte Nielsen, Boye S. Larsen, Jim S. Østerlind, Kell Nielsen, Svend E. Tarpgaard, Line S. Qvortrup, Camilla Pfeiffer, Per Holländer, Niels H. Keldsen, Nina Hansen, Torben F. Jensen, Brita B. Høgdall, Estrid V. S. Jensen, Benny V. Johansen, Julia S. PLoS One Research Article PURPOSE: We tested the hypothesis that expression of microRNAs (miRNAs) in cancer tissue can predict effectiveness of bevacizumab added to capecitabine and oxaliplatin (CAPEOX) in patients with metastatic colorectal cancer (mCRC). EXPERIMENTAL DESIGN: Patients with mCRC treated with first line CAPEOX and bevacizumab (CAPEOXBEV): screening (n = 212) and validation (n = 121) cohorts, or CAPEOX alone: control cohort (n = 127), were identified retrospectively and archival primary tumor samples were collected. Expression of 754 miRNAs was analyzed in the screening cohort using polymerase chain reaction (PCR) arrays and expression levels were related to time to disease progression (TTP) and overall survival (OS). Significant miRNAs from the screening study were analyzed in all three cohorts using custom PCR arrays. In situ hybridization (ISH) was done for selected miRNAs. RESULTS: In the screening study, 26 miRNAs were significantly correlated with outcome in multivariate analyses. Twenty-two miRNAs were selected for further study. Higher miR-664-3p expression and lower miR-455-5p expression were predictive of improved outcome in the CAPEOXBEV cohorts and showed a significant interaction with bevacizumab effectiveness. The effects were strongest for OS. Both miRNAs showed high expression in stromal cells. Higher expression of miR-196b-5p and miR-592 predicted improved outcome regardless of bevacizumab treatment, with similar effect estimates in all three cohorts. CONCLUSIONS: We have identified potentially predictive miRNAs for bevacizumab effectiveness and additional miRNAs that could be related to chemotherapy effectiveness or prognosis in patients with mCRC. Our findings need further validation in large cohorts, preferably from completed randomized trials. Public Library of Science 2014-10-15 /pmc/articles/PMC4198118/ /pubmed/25329796 http://dx.doi.org/10.1371/journal.pone.0109430 Text en © 2014 Boisen 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Boisen, Mogens K.
Dehlendorff, Christian
Linnemann, Dorte
Nielsen, Boye S.
Larsen, Jim S.
Østerlind, Kell
Nielsen, Svend E.
Tarpgaard, Line S.
Qvortrup, Camilla
Pfeiffer, Per
Holländer, Niels H.
Keldsen, Nina
Hansen, Torben F.
Jensen, Brita B.
Høgdall, Estrid V. S.
Jensen, Benny V.
Johansen, Julia S.
Tissue MicroRNAs as Predictors of Outcome in Patients with Metastatic Colorectal Cancer Treated with First Line Capecitabine and Oxaliplatin with or without Bevacizumab
title Tissue MicroRNAs as Predictors of Outcome in Patients with Metastatic Colorectal Cancer Treated with First Line Capecitabine and Oxaliplatin with or without Bevacizumab
title_full Tissue MicroRNAs as Predictors of Outcome in Patients with Metastatic Colorectal Cancer Treated with First Line Capecitabine and Oxaliplatin with or without Bevacizumab
title_fullStr Tissue MicroRNAs as Predictors of Outcome in Patients with Metastatic Colorectal Cancer Treated with First Line Capecitabine and Oxaliplatin with or without Bevacizumab
title_full_unstemmed Tissue MicroRNAs as Predictors of Outcome in Patients with Metastatic Colorectal Cancer Treated with First Line Capecitabine and Oxaliplatin with or without Bevacizumab
title_short Tissue MicroRNAs as Predictors of Outcome in Patients with Metastatic Colorectal Cancer Treated with First Line Capecitabine and Oxaliplatin with or without Bevacizumab
title_sort tissue micrornas as predictors of outcome in patients with metastatic colorectal cancer treated with first line capecitabine and oxaliplatin with or without bevacizumab
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4198118/
https://www.ncbi.nlm.nih.gov/pubmed/25329796
http://dx.doi.org/10.1371/journal.pone.0109430
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