MicroRNA signatures predict oestrogen receptor, progesterone receptor and HER2/neu receptor status in breast cancer.

Department of Surgery, Clinical Science Institute, University Hospital/National University of Ireland Galway, Galway, Ireland.
Breast cancer research: BCR (Impact Factor: 5.88). 06/2009; 11(3):R27. DOI: 10.1186/bcr2257
Source: PubMed

ABSTRACT Breast cancer is a heterogeneous disease encompassing a number of phenotypically diverse tumours. Expression levels of the oestrogen, progesterone and HER2/neu receptors which characterize clinically distinct breast tumours have been shown to change during disease progression and in response to systemic therapies. Mi(cro)RNAs play critical roles in diverse biological processes and are aberrantly expressed in several human neoplasms including breast cancer, where they function as regulators of tumour behaviour and progression. The aims of this study were to identify miRNA signatures that accurately predict the oestrogen receptor (ER), progesterone receptor (PR) and HER2/neu receptor status of breast cancer patients to provide insight into the regulation of breast cancer phenotypes and progression.
Expression profiling of 453 miRNAs was performed in 29 early-stage breast cancer specimens. miRNA signatures associated with ER, PR and HER2/neu status were generated using artificial neural networks (ANN), and expression of specific miRNAs was validated using RQ-PCR.
Stepwise ANN analysis identified predictive miRNA signatures corresponding 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) and HER2/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 and PR-negative tumours.
This study demonstrates that ANN analysis reliably identifies biologically relevant miRNAs associated with specific breast cancer phenotypes. The association of specific miRNAs with ER, PR and HER2/neu status indicates a role for these miRNAs in disease classification of breast cancer. Decreased expression of miR-342 in the therapeutically challenging triple-negative breast tumours, increased miR-342 expression in the luminal B tumours, and downregulated miR-520g in ER and PR-positive tumours indicates that not only is dysregulated miRNA expression a marker for poorer prognosis breast cancer, but that it could also present an attractive target for therapeutic intervention.

1 Bookmark
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: The role of miRNAs in familial breast cancer (fBC) is poorly investigated as also in the BRCA-like tumors. To identify a specific miRNA expression pattern which could allow a better fBC classification not only based on clinico-pathological and immunophenotypical parameters we analyzed miRNA profile in familial and sporadic samples. Moreover since BRCA1 tumors and sporadic triple negative (TN) breast tumors share similarities regarding clinical outcomes and some histological characteristics, we focused on TN and not TN cases. METHODS: The sample set included fresh frozen tissue samples, including 39 female fBCs (19 BRCA-related and 20 BRCAX) and 12 male fBC (BRCAX). Moreover, we considered TN and non TN (NTN), 21 BRCA-related and 27 sporadic BCs. MiRNA profiling was performed through GeneChip miRNA v.1.0 Array (Affymetrix). ANOVA, hierarchical and consensus clustering analyses allowed identification of pattern of expression of miRNAs and pathway enrichment analysis, considering validated target genes, was carried out to achieve a deeper biological understanding. RESULTS: ANOVA test led to the identification of 53 deregulated miRNAs; hierarchical and consensus clustering of female fBCs (fFBCs) and male fBCs (fMBCs) highlighted the presence of 3 sample clusters named FBC1, FBC2 and FBC3. We found a correlation between ER-status and the three sample clusters. The three clusters are distinct by a different expression of two clusters of miRNAs (CLU1 and CLU2), which resulted to be different in targeted pathways. In particular, CLU1 targets cellular pathways and CLU2 is involved in epigenetic activities. Considering TN and NTN BRCA-related and sporadic tumors, a hierarchical clustering identified two clusters of miRNAs, which were not so different from CLU1 and CLU2, both in miRNA content and targeted pathways. CONCLUSIONS: Our results highlighted the importance of miRNA regulation to better clarify similarities and differences between familial and sporadic BC groups.
    Journal of Translational Medicine 11/2014; · 3.99 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Breast cancer patients with positive estrogen receptor (ER) have a better prognosis. However, no prognostic miRNA signature was reported in the ER-positive breast cancer. The aim of the study was to identify and assess the prognostic significance of a miRNA signature in ER-positive breast cancer.Methods Two cohorts from The Cancer Genome Atlas (TCGA) dataset were used as training (n =596) and testing set (n =319). Differential expression profiling was identified in the training set. And the prognostic value of the miRNA signature was then assessed in the two cohorts.ResultsA total of 14 miRNAs were observed to be associated with the status of ER by significance analysis of microarrays (SAM) in the training set. Patients were characterized as high score or low score group according to the calculated risk scores from each miRNA. And patients in high score group had worse overall survival compared with those in low score group both in the training and testing set.Conclusions Our study revealed a miRNA signature including 14 miRNAs associated with ER status which could act as a prognostic marker in ER-positive breast cancer.
    Journal of Experimental & Clinical Cancer Research 11/2014; 33(1):94. · 3.27 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Aberrant expression of miRNAs contributes to HCC development. Here, we observed elevated miR-520g expression in tumor samples from HCC patients with relapse and metastasis, and this high miR-520g expression was correlated with poor survival. Through gain- and loss-of-function studies, miR-520g was demonstrated to facilitate HCC cell migration, invasion and epithelial-mesenchymal transition (EMT). SMAD7 was identified as a direct target of miR-520g. Accordingly, we conclude that high miR-520g expression promotes HCC cell mobility and EMT by targeting SMAD7, and this is correlated with reduced survival in HCC patients. Copyright © 2014. Published by Elsevier B.V.
    FEBS Letters 11/2014; · 3.34 Impact Factor

Full-text (3 Sources)

Available from
May 19, 2014