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dc.contributor.authorMcDermott, Ailbhe M.
dc.contributor.authorMiller, Nicola
dc.contributor.authorWall, Deirdre
dc.contributor.authorMartyn, Lorcan M.
dc.contributor.authorBall, Graham
dc.contributor.authorSweeney, Karl J.
dc.contributor.authorKerin, Michael J.
dc.identifier.citationMcDermott, Ailbhe M. Miller, Nicola; Wall, Deirdre; Martyn, Lorcan M.; Ball, Graham; Sweeney, Karl J.; Kerin, Michael J. (2014). Identification and validation of oncologic mirna biomarkers for luminal a-like breast cancer. PLoS ONE 9 (1),
dc.description.abstractIntroduction: 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.
dc.publisherPublic Library of Science (PLoS)
dc.relation.ispartofPLoS ONE
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Ireland
dc.subjectblood-based markers
dc.subjectcirculating micrornas
dc.titleIdentification and validation of oncologic mirna biomarkers for luminal a-like breast cancer

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