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

El Ansari, Rokaya and Craze, Madeleine L. and Diez-Rodriguez, Maria and Nolan, Christopher C. and Ellis, Ian O. and Rakha, Emad A. and Green, Andrew R. (2018) The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes. British Journal of Cancer, 118 . pp. 1115-1122. ISSN 1532-1827

[img]
Preview
PDF - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Download (3MB) | Preview

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.

Item Type: Article
Keywords: SLC3A2; Breast cancer; Prognosis
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Cancer and Stem Cells
Identification Number: https://doi.org/10.1038/s41416-018-0038-5
Depositing User: Eprints, Support
Date Deposited: 16 Mar 2018 13:15
Last Modified: 16 Sep 2018 04:30
URI: http://eprints.nottingham.ac.uk/id/eprint/49376

Actions (Archive Staff Only)

Edit View Edit View