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The combined expression of solute carriers is associated with a poor prognosis in highly proliferative ER+ breast cancer

El-Ansari, Rokaya, Craze, Madeleine L., Alfarsi, Lutfi, Soria, Daniele, Diez-Rodriguez, Maria, Nolan, Christopher C., Ellis, Ian O., Rakha, Emad A., Green, Andrew R. (2019) The combined expression of solute carriers is associated with a poor prognosis in highly proliferative ER+ breast cancer. Breast cancer research and treatment, 175 (1). pp. 27-38. ISSN 0167-6806. E-ISSN 1573-7217. (doi:10.1007/s10549-018-05111-w) (KAR id:77038)

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https://dx.doi.org/10.1007/s10549-018-05111-w

Abstract

Purpose: Breast cancer (BC) is a heterogeneous disease characterised by variant biology, metabolic activity, and patient outcome. Glutamine availability for growth and progression of BC is important in several BC subtypes. This study aimed to evaluate the biological and prognostic role of the combined expression of key glutamine transporters, SLC1A5, SLC7A5 and SLC3A2 in BC with emphasis on the intrinsic molecular subtypes.

Results: Clustering analysis of SLC1A5, SLC7A5 and SLC3A2 identified three clusters Low SLCs (SLC1A5-/SLC7A5-/SLC3A2-), High SLC1A5 (SLC1A5+/SLC7A5-/SLC3A2-) and High SLCs (SLC1A5+/SLC7A5+/SLC3A2+) which had distinct correlations to known prognostic factors and patient outcome (p<0.001). The key regulator of tumour cell metabolism, c-MYC, was significantly expressed in tumours in the High SLCs cluster (p<0.001). When different BC subtypes were considered, the association with the poor outcome was observed in the ER+ high proliferation/luminal B class only (p= 0.003). In multivariate analysis, SLC clusters were independent risk factor for shorter breast cancer specific survival (p= 0.001).

Conclusion: The co-operative expression of SLC1A5, SLC7A5 and SLC3A2 appears to play a role in the aggressive subclass of ER+ high proliferation/ luminal BC, driven by c-MYC, and therefore have the potential to act as therapeutic targets, particularly in synergism.

Item Type: Article
DOI/Identification number: 10.1007/s10549-018-05111-w
Uncontrolled keywords: SLC1A5, SLC7A5, SLC3A2, clusters, breast cancer, prognosis
Subjects: R Medicine > RC Internal medicine > RC254 Neoplasms. Tumors. Oncology
Divisions: Faculties > Sciences > School of Computing > Data Science
Depositing User: Daniele Soria
Date Deposited: 04 Oct 2019 08:42 UTC
Last Modified: 21 Jan 2020 00:00 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/77038 (The current URI for this page, for reference purposes)
Soria, Daniele: https://orcid.org/0000-0002-0164-8218
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