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.

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: Aug 29, 2022
• Journal: Breast Cancer Research and Treatment
• Print ISSN: 0167-6806
• Electronic ISSN: 1573-7217
• Publisher: Springer Verlag
• 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