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Utility of ankyrin 3 as a prognostic marker in androgen-receptor-positive breast cancer

  • Sasagu Kurozumi
  • Chitra Joseph
  • Sara Raafat
  • Sultan Sonbul
  • Yousif Kariri
  • Sami Alsaeed
  • Marian Pigera
  • Mansour Alsaleem
  • Christopher C. Nolan
  • Simon J. Johnston
  • Mohammed A. Aleskandarany
  • Angela Ogden
  • Takaaki Fujii
  • Ken Shirabe
  • Stewart G. Martin
  • Ibraheem Alshankyty
  • Nigel P. Mongan
  • Ian O. Ellis
  • Andrew R. Green
  • Emad A. RakhaEmail author
Preclinical study

Abstract

Purpose

Androgen receptor (AR) and AR signaling pathways are thought to play a role in breast cancer (BC) and are potentially related to treatment responses and outcomes. Ankyrin 3 (ANK3) is associated with AR stability in cancer cells. In the present study, we investigated the clinicopathological utility of ANK3 expression with emphasis on AR and its associated signalling pathway at transcriptomic and proteomic phases.

Patients and methods

The Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort (n = 1980) and The Cancer Genome Atlas (TCGA) dataset (n = 1039) were used to assess the expression and significance of ANK3 mRNA and other AR signalling pathway-associated gene signature. Using immunohistochemistry, ANK3 protein expression was evaluated in large (n = 982) cohort of early-stage BC with long-term follow-up and compared with clinicopathological characteristics and its prognostic value in the whole cohort and the subgroups stratified by AR protein expression.

Results

An AR-related gene signature was developed, comprising 20 genes, which included ANK3. This AR-related gene signature was significantly associated with AR mRNA expression, oestrogen receptor, human epidermal growth factor receptor 2 (HER2) status and the patients’ outcomes. In tumours with high AR protein expression (n = 614), high ANK3 protein expression was significantly associated with progesterone receptor positivity and it was independently associated with the good outcomes (p = 0.025).

Conclusions

This study indicates that ANK3 is related to AR signalling pathway and is associated with BC prognosis.

Keywords

Invasive breast cancer Androgen receptor Ankyrin 3 Prognostic marker 

Notes

Acknowledgements

We thank the Nottingham Health Science Biobank and Breast Cancer Now Tissue Bank for the provision of tissue samples.

Funding

This study was funded by the University of Nottingham (Nottingham Life Cycle 6).

Compliance with ethical standards

Conflict of interest

Ibraheem Alshankyty is a consultant/advisory board in Molecular Diagnostics Lab, College of Applied Med. Sci., KAU. All authors of this work declare that they have no conflict of interest.

Ethical approval

This study was approved by the Nottingham Research Ethics Committee 2 (Reference title: Development of a molecular genetic classification of breast cancer). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from the participants included in the study.

Supplementary material

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Sasagu Kurozumi
    • 1
    • 2
  • Chitra Joseph
    • 1
  • Sara Raafat
    • 1
    • 3
  • Sultan Sonbul
    • 1
  • Yousif Kariri
    • 1
  • Sami Alsaeed
    • 1
  • Marian Pigera
    • 1
  • Mansour Alsaleem
    • 1
  • Christopher C. Nolan
    • 1
  • Simon J. Johnston
    • 1
  • Mohammed A. Aleskandarany
    • 1
    • 4
  • Angela Ogden
    • 1
  • Takaaki Fujii
    • 2
  • Ken Shirabe
    • 2
  • Stewart G. Martin
    • 1
  • Ibraheem Alshankyty
    • 5
  • Nigel P. Mongan
    • 6
    • 7
  • Ian O. Ellis
    • 1
  • Andrew R. Green
    • 1
  • Emad A. Rakha
    • 1
    • 4
    • 8
    Email author
  1. 1.Division of Cancer and Stem Cells, Nottingham Breast Cancer Research Centre, School of MedicineUniversity of NottinghamNottinghamUK
  2. 2.Department of General Surgical ScienceGunma University Graduate School of MedicineGunmaJapan
  3. 3.Department of Pathology, Faculty of MedicineMansoura UniversityMansouraEgypt
  4. 4.Faculty of MedicineMenoufyia UniversityShebin El KomEgypt
  5. 5.Faculty of Applied Medical SciencesKing Abdulaziz UniversityJeddahSaudi Arabia
  6. 6.Cancer Biology and Translational Research, Faculty of Medicine and Health SciencesUniversity of NottinghamNottinghamUK
  7. 7.Department of PharmacologyWeill Cornell MedicineNew YorkUSA
  8. 8.Division of Cancer and Stem Cells, Department of Histopathology, School of MedicineThe University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham City HospitalNottinghamUK

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