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A novel panel of differentially-expressed microRNAs in breast cancer brain metastasis may predict patient survival

Breast cancer brain metastasis (BCBM) is an area of unmet clinical need. MicroRNAs (miRNAs) have been linked to the metastatic process in breast cancer (BC). In this study, we aim to determine differentially-expressed miRNAs utilising primary BCs that did not relapse (BCNR, n = 12), primaries that r...

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Autores principales: Giannoudis, Athina, Clarke, Kim, Zakaria, Rasheed, Varešlija, Damir, Farahani, Mosavar, Rainbow, Lucille, Platt-Higgins, Angela, Ruthven, Stuart, Brougham, Katherine A., Rudland, Philip S., Jenkinson, Michael D., Young, Leonie S., Falciani, Francesco, Palmieri, Carlo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6897960/
https://www.ncbi.nlm.nih.gov/pubmed/31811234
http://dx.doi.org/10.1038/s41598-019-55084-z
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author Giannoudis, Athina
Clarke, Kim
Zakaria, Rasheed
Varešlija, Damir
Farahani, Mosavar
Rainbow, Lucille
Platt-Higgins, Angela
Ruthven, Stuart
Brougham, Katherine A.
Rudland, Philip S.
Jenkinson, Michael D.
Young, Leonie S.
Falciani, Francesco
Palmieri, Carlo
author_facet Giannoudis, Athina
Clarke, Kim
Zakaria, Rasheed
Varešlija, Damir
Farahani, Mosavar
Rainbow, Lucille
Platt-Higgins, Angela
Ruthven, Stuart
Brougham, Katherine A.
Rudland, Philip S.
Jenkinson, Michael D.
Young, Leonie S.
Falciani, Francesco
Palmieri, Carlo
author_sort Giannoudis, Athina
collection PubMed
description Breast cancer brain metastasis (BCBM) is an area of unmet clinical need. MicroRNAs (miRNAs) have been linked to the metastatic process in breast cancer (BC). In this study, we aim to determine differentially-expressed miRNAs utilising primary BCs that did not relapse (BCNR, n = 12), primaries that relapsed (BCR) and their paired (n = 40 pairs) brain metastases (BM) using the NanoString™ nCounter™ miRNA Expression Assays. Significance analysis of microarrays identified 58 and 11 differentially-expressed miRNAs between BCNR vs BCR and BCR vs BM respectively and pathway analysis revealed enrichment for genes involved in invasion and metastasis. Four miRNAs, miR-132-3p, miR-199a-5p, miR-150-5p and miR-155-5p, were differentially-expressed within both cohorts (BCNR-BCR, BCR-BM) and receiver-operating characteristic curve analysis (p = 0.00137) and Kaplan-Meier survival method (p = 0.0029, brain metastasis-free survival; p = 0.0007, overall survival) demonstrated their potential use as prognostic markers. Ingenuity pathway enrichment linked them to the MET oncogene, and the cMET protein was overexpressed in the BCR (p < 0.0001) and BM (p = 0.0008) cases, compared to the BCNRs. The 4-miRNAs panel identified in this study could be potentially used to distinguish BC patients with an increased risk of developing BCBM and provide potential novel therapeutic targets, whereas cMET-targeting warrants further investigation in the treatment of BCBM.
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spelling pubmed-68979602019-12-12 A novel panel of differentially-expressed microRNAs in breast cancer brain metastasis may predict patient survival Giannoudis, Athina Clarke, Kim Zakaria, Rasheed Varešlija, Damir Farahani, Mosavar Rainbow, Lucille Platt-Higgins, Angela Ruthven, Stuart Brougham, Katherine A. Rudland, Philip S. Jenkinson, Michael D. Young, Leonie S. Falciani, Francesco Palmieri, Carlo Sci Rep Article Breast cancer brain metastasis (BCBM) is an area of unmet clinical need. MicroRNAs (miRNAs) have been linked to the metastatic process in breast cancer (BC). In this study, we aim to determine differentially-expressed miRNAs utilising primary BCs that did not relapse (BCNR, n = 12), primaries that relapsed (BCR) and their paired (n = 40 pairs) brain metastases (BM) using the NanoString™ nCounter™ miRNA Expression Assays. Significance analysis of microarrays identified 58 and 11 differentially-expressed miRNAs between BCNR vs BCR and BCR vs BM respectively and pathway analysis revealed enrichment for genes involved in invasion and metastasis. Four miRNAs, miR-132-3p, miR-199a-5p, miR-150-5p and miR-155-5p, were differentially-expressed within both cohorts (BCNR-BCR, BCR-BM) and receiver-operating characteristic curve analysis (p = 0.00137) and Kaplan-Meier survival method (p = 0.0029, brain metastasis-free survival; p = 0.0007, overall survival) demonstrated their potential use as prognostic markers. Ingenuity pathway enrichment linked them to the MET oncogene, and the cMET protein was overexpressed in the BCR (p < 0.0001) and BM (p = 0.0008) cases, compared to the BCNRs. The 4-miRNAs panel identified in this study could be potentially used to distinguish BC patients with an increased risk of developing BCBM and provide potential novel therapeutic targets, whereas cMET-targeting warrants further investigation in the treatment of BCBM. Nature Publishing Group UK 2019-12-06 /pmc/articles/PMC6897960/ /pubmed/31811234 http://dx.doi.org/10.1038/s41598-019-55084-z Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Giannoudis, Athina
Clarke, Kim
Zakaria, Rasheed
Varešlija, Damir
Farahani, Mosavar
Rainbow, Lucille
Platt-Higgins, Angela
Ruthven, Stuart
Brougham, Katherine A.
Rudland, Philip S.
Jenkinson, Michael D.
Young, Leonie S.
Falciani, Francesco
Palmieri, Carlo
A novel panel of differentially-expressed microRNAs in breast cancer brain metastasis may predict patient survival
title A novel panel of differentially-expressed microRNAs in breast cancer brain metastasis may predict patient survival
title_full A novel panel of differentially-expressed microRNAs in breast cancer brain metastasis may predict patient survival
title_fullStr A novel panel of differentially-expressed microRNAs in breast cancer brain metastasis may predict patient survival
title_full_unstemmed A novel panel of differentially-expressed microRNAs in breast cancer brain metastasis may predict patient survival
title_short A novel panel of differentially-expressed microRNAs in breast cancer brain metastasis may predict patient survival
title_sort novel panel of differentially-expressed micrornas in breast cancer brain metastasis may predict patient survival
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6897960/
https://www.ncbi.nlm.nih.gov/pubmed/31811234
http://dx.doi.org/10.1038/s41598-019-55084-z
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