Maryam Althobiti
Oestrogen-regulated protein SLC39A6: a biomarker of good prognosis in luminal breast cancer
Althobiti, Maryam; El-Sharawy, Khloud A.; Joseph, Chitra; Aleskandarany, Mohammed; Toss, Michael S.; Green, Andrew R.; Rakha, Emad A.
Authors
Khloud A. El-Sharawy
Dr CHITRA JOSEPH CHITRA.JOSEPH@NOTTINGHAM.AC.UK
Research Fellow
Mohammed Aleskandarany
Michael S. Toss
ANDREW GREEN ANDREW.GREEN@NOTTINGHAM.AC.UK
Associate Professor
EMAD RAKHA Emad.Rakha@nottingham.ac.uk
Professor of Breast Cancer Pathology
Abstract
Purpose
The outcome of the luminal oestrogen receptor-positive (ER +) subtype of breast cancer (BC) is highly variable and patient stratification needs to be refined. We assessed the prognostic significance of oestrogen-regulated solute carrier family 39 member 6 (SLC39A6) in BC, with emphasis on ER + tumours.
Materials and methods
SLC39A6 mRNA expression and copy number alterations were assessed using the METABRIC cohort (n = 1980). SLC39A6 protein expression was evaluated in a large (n = 670) and annotated series of early-stage (I–III) operable BC using tissue microarrays and immunohistochemistry. The associations between SLC39A6 expression and clinicopathological parameters, patient outcomes and other ER-related markers were evaluated using Chi-square tests and Kaplan–Meier curves.
Results
High SLC39A6 mRNA and protein expression was associated with features characteristic of less aggressive tumours in the entire BC cohort and ER + subgroup. SLC39A6 protein expression was detected in the cytoplasm and nuclei of the tumour cells. High SLC39A6 nuclear expression and mRNA levels were positively associated with ER + tumours and expression of ER-related markers, including the progesterone receptor, forkhead box protein A1 and GATA binding protein 3. In the ER + luminal BC, high SLC39A6 expression was independently associated with longer BC-specific survival (BCSS) (P = 0.015, HR 0.678, 95% CI 0.472‒0.972) even in those who did not receive endocrine therapy (P = 0.001, HR 0.701, 95% CI 0.463‒1.062).
Conclusion
SLC39A6 may be prognostic for a better outcome in ER + luminal BC. Further functional studies to investigate the role of SLC39A6 in ER + luminal BC are warranted.
Citation
Althobiti, M., El-Sharawy, K. A., Joseph, C., Aleskandarany, M., Toss, M. S., Green, A. R., & Rakha, E. A. (2021). Oestrogen-regulated protein SLC39A6: a biomarker of good prognosis in luminal breast cancer. Breast Cancer Research and Treatment, 189(3), 621-630. https://doi.org/10.1007/s10549-021-06336-y
Journal Article Type | Article |
---|---|
Acceptance Date | Jul 15, 2021 |
Online Publication Date | Aug 28, 2021 |
Publication Date | 2021-10 |
Deposit Date | Jul 19, 2021 |
Publicly Available Date | Mar 28, 2024 |
Journal | Breast Cancer Research and Treatment |
Print ISSN | 0167-6806 |
Electronic ISSN | 1573-7217 |
Peer Reviewed | Peer Reviewed |
Volume | 189 |
Issue | 3 |
Pages | 621-630 |
DOI | https://doi.org/10.1007/s10549-021-06336-y |
Public URL | https://nottingham-repository.worktribe.com/output/5805639 |
Publisher URL | https://link.springer.com/article/10.1007/s10549-021-06336-y |
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Oestrogen-regulated protein SLC39A6: a biomarker of good prognosis in luminal breast cancer
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Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/
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