41598_2019_Article_55084.pdf (2.01 MB)
A novel panel of differentially-expressed microRNAs in breast cancer brain metastasis may predict patient survival.
journal contributionposted on 2020-12-16, 17:11 authored by Athina Giannoudis, Kim Clarke, Rasheed Zakaria, Damir VareslijaDamir Vareslija, Mosavar Farahani, Lucille Rainbow, Angela Platt-Higgins, Stuart Ruthven, Katherine A Brougham, Philip S Rudland, Michael D Jenkinson, Leonie YoungLeonie Young, Francesco Falciani, Carlo Palmieri
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.
Associated research data filesData available at the publisher's website: https://doi.org/10.1038/s41598-019-55084-z
CommentsThe original article is available at https://www.nature.com/
Published CitationGiannoudis A, Clarke K, Zakaria R, Varešlija D, Farahani M, Rainbow L, Platt-Higgins A, Ruthven S, Brougham KA, Rudland PS, Jenkinson MD, Young LS, Falciani F, Palmieri C. A novel panel of differentially-expressed microRNAs in breast cancer brain metastasis may predict patient survival. Scientific Reports. 2019;9(1):18518.
Publication Date6 December 2019
PublisherNature Publishing Group
- Published Version (Version of Record)