Experiment Detail



Experiment IDEXP00085
ReferenceTitle: MicroRNA signatures predict oestrogen receptor, progesterone receptor andHER2/neu receptor status in breast cancer.
Author: Lowery AJ, Miller N, Devaney A, McNeill RE, Davoren PA, Lemetre C, Benes V,Schmidt S, Blake J, Ball G, Kerin MJ.
Journal: Breast Cancer Res. 2009;11(3):R27. doi: 10.1186/bcr2257. Epub 2009 May 11.
Abstract: INTRODUCTION: Breast cancer is a heterogeneous disease encompassing a number ofphenotypically diverse tumours. Expression levels of the oestrogen, progesterone and HER2/neu receptors which characterize clinically distinct breast tumours havebeen shown to change during disease progression and in response to systemictherapies. Mi(cro)RNAs play critical roles in diverse biological processes andare aberrantly expressed in several human neoplasms including breast cancer,where they function as regulators of tumour behaviour and progression. The aimsof this study were to identify miRNA signatures that accurately predict theoestrogen receptor (ER), progesterone receptor (PR) and HER2/neu receptor status of breast cancer patients to provide insight into the regulation of breast cancerphenotypes and progression.METHODS: Expression profiling of 453 miRNAs was performed in 29 early-stagebreast cancer specimens. miRNA signatures associated with ER, PR and HER2/neustatus were generated using artificial neural networks (ANN), and expression ofspecific miRNAs was validated using RQ-PCR.RESULTS: Stepwise ANN analysis identified predictive miRNA signaturescorresponding with oestrogen (miR-342, miR-299, miR-217, miR-190, miR-135b,miR-218), progesterone (miR-520g, miR-377, miR-527-518a, miR-520f-520c) andHER2/neu (miR-520d, miR-181c, miR-302c, miR-376b, miR-30e) receptor status.MiR-342 and miR-520g expression was further analysed in 95 breast tumours.MiR-342 expression was highest in ER and HER2/neu-positive luminal B tumours and lowest in triple-negative tumours. MiR-520g expression was elevated in ER andPR-negative tumours.CONCLUSIONS: This study demonstrates that ANN analysis reliably identifiesbiologically relevant miRNAs associated with specific breast cancer phenotypes.The association of specific miRNAs with ER, PR and HER2/neu status indicates arole for these miRNAs in disease classification of breast cancer. Decreasedexpression of miR-342 in the therapeutically challenging triple-negative breasttumours, increased miR-342 expression in the luminal B tumours, and downregulatedmiR-520g in ER and PR-positive tumours indicates that not only is dysregulatedmiRNA expression a marker for poorer prognosis breast cancer, but that it couldalso present an attractive target for therapeutic intervention.
PMID: 19432961
Expressiion ProfileDescription: MicroRNA signatures predict Estrogen receptor, Progesterone receptor and HER2/neu receptor status in Breast Cancer
Organism: Homo sapiens
GEO ID: GSE15885
Platform: GPL6127
Number of samples: 29
Design and SampleCancer Type: breast cancer
Cancer SubType: ER positive
Cell Line: N/D
Experimental Design: subtype1 vs substype2
Case Sample: ER positive breast tumour
Control Sample: ER negative breast cancer
Num of Case: 16
Num of Control: 13
Quantification Software: Limma
Num of miRNAs: 295
IdentificationNum of Up: 1
Num of Down: 0