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

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.