The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes

El Ansari, Rokaya; Craze, Madeleine L.; Diez-Rodriguez, Maria; Nolan, Christopher C.; Ellis, Ian O.; Rakha, Emad A.; Green, Andrew R.

Abstract

Background: Breast cancer (BC) is a heterogeneous disease characterised by variant biology, metabolic activity and patient outcome. This study aimed to evaluate the biological and prognostic value of the membrane solute carrier, SLC3A2 in BC with emphasis on the intrinsic molecular subtypes.

Methods: SLC3A2 was assessed at the genomic level, using METABRIC data (n=1,980), and proteomic level, using immunohistochemistry on TMA sections constructed from a large well-characterised primary BC cohort (n=2,500). SLC3A2 expression was correlated with clinicopathological parameters, molecular subtypes, and patient outcome.

Results: SLC3A2 mRNA and protein expression were strongly correlated with higher tumour grade and poor Nottingham prognostic index (NPI). High expression of SLC3A2 was observed in triple negative (TN), HER2+, and ER+ high proliferation subtypes. SLC3A2 mRNA and protein expression were significantly associated with the expression of c-MYC in all BC subtypes (p<0.001). High expression of SLC3A2 protein was associated with poor patient outcome (p<0.001)), but only in the ER+ high proliferation (p=0.01) and triple negative (p=0.04) subtypes. In multivariate analysis SLC3A2 protein was an independent risk factor for shorter breast cancer specific survival (p<0.001).

Conclusions: SLC3A2 appears to play a role in the aggressive BC subtypes driven by MYC and could act as a potential prognostic marker. Functional assessment is necessary to reveal its potential therapeutic value in the different BC subtypes.

Citation

El Ansari, R., Craze, M. L., Diez-Rodriguez, M., Nolan, C. C., Ellis, I. O., Rakha, E. A., & Green, A. R. (2018). The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes. British Journal of Cancer, 118(8), 1115-1122. https://doi.org/10.1038/s41416-018-0038-5

• Journal Article Type: Article
• Acceptance Date: Jan 25, 2018
• Online Publication Date: Mar 16, 2018
• Publication Date: 2018-04
• Deposit Date: Mar 16, 2018
• Publicly Available Date: Sep 17, 2019
• Journal: British Journal of Cancer
• Print ISSN: 0007-0920
• Electronic ISSN: 1532-1827
• Publisher: Cancer Research UK
• Peer Reviewed: Peer Reviewed
• Volume: 118
• Issue: 8
• Pages: 1115-1122
• DOI: https://doi.org/10.1038/s41416-018-0038-5
• Keywords: SLC3A2; Breast cancer; Prognosis
• Public URL: https://nottingham-repository.worktribe.com/output/920142
• Publisher URL: https://www.nature.com/articles/s41416-018-0038-5
• Contract Date: Mar 16, 2018