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



Giannoudis, Athina ORCID: 0000-0002-7200-1497, Clarke, Kim, Zakaria, Rasheed ORCID: 0000-0001-6826-2662, Vareslija, Damir, Farahani, Mosavar, Rainbow, Lucille ORCID: 0000-0003-0447-6885, Platt-Higgins, Angela, Ruthven, Stuart, Brougham, Katherine A, Rudland, Philip S ORCID: 0000-0002-7491-0846
et al (show 4 more authors) (2019) A novel panel of differentially-expressed microRNAs in breast cancer brain metastasis may predict patient survival. SCIENTIFIC REPORTS, 9 (1). 18518-.

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: Humans, Breast Neoplasms, Brain Neoplasms, Neoplasm Invasiveness, Neoplasm Recurrence, Local, MicroRNAs, Prognosis, Treatment Outcome, Oligonucleotide Array Sequence Analysis, Risk, Normal Distribution, ROC Curve, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Principal Component Analysis, Female, Kaplan-Meier Estimate, Biomarkers, Tumor
Depositing User: Symplectic Admin
Date Deposited: 12 Dec 2019 10:08
Last Modified: 19 Jan 2023 00:12
DOI: 10.1038/s41598-019-55084-z
Open Access URL: http://10.0.4.14/s41598-019-55084-z
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3066066