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FOXA2 mRNA expression is associated with relapse in patients with Triple-Negative/Basal-like breast carcinoma

Breast Cancer Research and Treatment volume 153, pages 465–474 (2015)Cite this article

Abstract

The FOXA family of transcription factors regulates chromatin structure and gene expression especially during embryonic development. In normal breast tissue FOXA1 acts throughout mammary development; whereas in breast carcinoma its expression promotes luminal phenotype and correlates with good prognosis. However, the role of FOXA2 has not been previously studied in breast cancer. Our purpose was to analyze the expression of FOXA2 in breast cancer cells, to explore its role in breast cancer stem cells, and to correlate its mRNA expression with clinicopathological features and outcome in a series of patients diagnosed with breast carcinoma. We analyzed FOXA2 mRNA expression in a retrospective cohort of 230 breast cancer patients and in cell lines. We also knocked down FOXA2 mRNA expression by siRNA to determine the impact on cell proliferation and mammospheres formation using a cancer stem cells culture assay. In vitro studies demonstrated higher FOXA2 mRNA expression in Triple-Negative/Basal-like cells. Further, when it was knocked down, cells decreased proliferation and its capability of forming mammospheres. Similarly, FOXA2 mRNA expression was detected in 10 % (23/230) of the tumors, especially in Triple-Negative/Basal-like phenotype (p < 0.001, Fisher’s test). Patients whose tumors expressed FOXA2 had increased relapses (59 vs. 79 %, p = 0.024, log-rank test) that revealed an independent prognostic value (HR = 3.29, C.I.95 % = 1.45–7.45, p = 0.004, Cox regression). Our results suggest that FOXA2 promotes cell proliferation, maintains cancer stem cells, favors the development of Triple-Negative/Basal-like tumors, and is associated with increase relapses.

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Abbreviations

CK:

Citokeratine

CSC:

Cancer stem cell

DFS:

Disease-free survival

EGFR:

Epidermal growth factor receptor

FFPE:

Formalin-fixed paraffin-embedded

HR:

Hormonal receptor

IHC:

Immunohistochemistry

OS:

Overall survival

qRT-PCR:

Quantitative real-time PCR

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Acknowledgments

We thank Mrs Doreen Dennecker for the revision of this manuscript, and Laura Andreu for their technical assistance.

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Authors and Affiliations

  1. Research Unit, Hospital General Universitari d’Alacant, C/Pintor Baeza 12, 03010, Alacant, Spain

    Ariadna Perez-Balaguer, Fernando Ortiz-Martínez, Araceli García-Martínez, Critina Pomares-Navarro & Gloria Peiró

  2. Department of Pathology, Hospital de la Santa Creu i Sant Pau, C/Sant Quintí 87-89, 08041, Barcelona, Spain

    Enrique Lerma

  3. Pathology Department, University General Hospital of Alicante, Alicante, Spain

    Gloria Peiró

  4. Institute of Bioengineering of Catalonia, C/Baldiri Reixac, 15–21, 08028, Barcelona, Catalonia, Spain

    Ariadna Perez-Balaguer

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  1. Ariadna Perez-Balaguer
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Correspondence to Ariadna Perez-Balaguer.

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Perez-Balaguer, A., Ortiz-Martínez, F., García-Martínez, A. et al. FOXA2 mRNA expression is associated with relapse in patients with Triple-Negative/Basal-like breast carcinoma. Breast Cancer Res Treat 153, 465–474 (2015). https://doi.org/10.1007/s10549-015-3553-6

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  • DOI: https://doi.org/10.1007/s10549-015-3553-6

Keywords

  • Breast carcinoma
  • Cancer stem cells
  • FOXA2
  • Prognosis