Oestrogen-regulated protein SLC39A6: a biomarker of good prognosis in luminal breast cancer

Journal article


Althobiti, M., El-sharawy, K. A., Joseph, C., Aleskandarany, M., Toss, M. S., Green, A. R. and Rakha, E. A. 2021. Oestrogen-regulated protein SLC39A6: a biomarker of good prognosis in luminal breast cancer. Breast Cancer Research and Treatment. 189 (3), pp. 621-630. https://doi.org/10.1007/s10549-021-06336-y
AuthorsAlthobiti, M., El-sharawy, K. A., Joseph, C., Aleskandarany, M., Toss, M. S., Green, A. R. and Rakha, E. A.
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.

KeywordsER-positive breast cancer; ER-related marker; Prognosis; SLC39A6
Year2021
JournalBreast Cancer Research and Treatment
Journal citation189 (3), pp. 621-630
PublisherSpringer
ISSN1573-7217
Digital Object Identifier (DOI)https://doi.org/10.1007/s10549-021-06336-y
Web address (URL)https://link.springer.com/article/10.1007/s10549-021-06336-y
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Open
Output statusPublished
Publication dates
Online28 Aug 2021
Publication process dates
Accepted15 Jul 2021
Deposited05 Nov 2024
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Open
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