McDermott, AM, Miller, N, Wall, D, Martyn, LM, Ball, G ORCID: https://orcid.org/0000-0001-5828-7129, Sweeney, KJ and Kerin, MJ, 2014. Identification and validation of oncologic miRNA biomarkers for Luminal A-like breast cancer. PLoS ONE, 9 (1), e87032. ISSN 1932-6203
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Abstract
Introduction: Breast cancer is a common disease with distinct tumor subtypes phenotypically characterized by ER and HER2/neu receptor status. MiRNAs play regulatory roles in tumor initiation and progression, and altered miRNA expression has been demonstrated in a variety of cancer states presenting the potential for exploitation as cancer biomarkers. Blood provides an excellent medium for biomarker discovery. This study investigated systemic miRNAs differentially expressed in Luminal A-like (ER+PR+HER2/neu-) breast cancer and their effectiveness as oncologic biomarkers in the clinical setting. Methods: Blood samples were prospectively collected from patients with Luminal A-like breast cancer (n=54) and controls (n=56). RNA was extracted, reverse transcribed and subjected to microarray analysis (n=10 Luminal A-like; n=10 Control). Differentially expressed miRNAs were identified by artificial neural network (ANN) data-mining algorithms. Expression of specific miRNAs was validated by RQ-PCR (n=44 Luminal A; n=46 Control) and potential relationships between circulating miRNA levels and clinicopathological features of breast cancer were investigated. Results: Microarray analysis identified 76 differentially expressed miRNAs. ANN revealed 10 miRNAs for further analysis ( miR-19b, miR-29a, miR-93, miR-181a, miR-182, miR-223, miR-301a, miR-423-5p, miR-486-5 and miR-652 ). The biomarker potential of 4 miRNAs ( miR-29a, miR-181a , miR-223 and miR-652 ) was confirmed by RQ-PCR, with significantly reduced expression in blood of women with Luminal A-like breast tumors compared to healthy controls (p=0.001, 0.004, 0.009 and 0.004 respectively). Binary logistic regression confirmed that combination of 3 of these miRNAs ( miR-29a, miR-181a and miR-652 ) could reliably differentiate between cancers and controls with an AUC of 0.80. Conclusion: This study provides insight into the underlying molecular portrait of Luminal A-like breast cancer subtype. From an initial 76 miRNAs, 4 were validated with altered expression in the blood of women with Luminal A-like breast cancer. The expression profiles of these 3 miRNAs, in combination with mammography, has potential to facilitate accurate subtype- specific breast tumor detection.
Item Type: | Journal article |
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Publication Title: | PLoS ONE |
Creators: | McDermott, A.M., Miller, N., Wall, D., Martyn, L.M., Ball, G., Sweeney, K.J. and Kerin, M.J. |
Publisher: | Public Library of Science |
Date: | 2014 |
Volume: | 9 |
Number: | 1 |
ISSN: | 1932-6203 |
Identifiers: | Number Type 10.1371/journal.pone.0087032 DOI |
Divisions: | Schools > School of Science and Technology |
Record created by: | EPrints Services |
Date Added: | 09 Oct 2015 10:08 |
Last Modified: | 09 Jun 2017 13:19 |
URI: | https://irep.ntu.ac.uk/id/eprint/8267 |
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