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

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. Meth...

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Main Authors: El Ansari, Rokaya, Craze, Madeleine L., Diez-Rodriguez, Maria, Nolan, Christopher C., Ellis, Ian O., Rakha, Emad A., Green, Andrew R.
Format: Article
Published: Cancer Research UK 2018
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Online Access:https://eprints.nottingham.ac.uk/49376/
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author El Ansari, Rokaya
Craze, Madeleine L.
Diez-Rodriguez, Maria
Nolan, Christopher C.
Ellis, Ian O.
Rakha, Emad A.
Green, Andrew R.
author_facet El Ansari, Rokaya
Craze, Madeleine L.
Diez-Rodriguez, Maria
Nolan, Christopher C.
Ellis, Ian O.
Rakha, Emad A.
Green, Andrew R.
author_sort El Ansari, Rokaya
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-493762024-08-15T15:27:23Z https://eprints.nottingham.ac.uk/49376/ 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. 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. Cancer Research UK 2018-03-16 Article PeerReviewed El Ansari, Rokaya, Craze, Madeleine L., Diez-Rodriguez, Maria, Nolan, Christopher C., Ellis, Ian O., 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 SLC3A2; Breast cancer; Prognosis https://www.nature.com/articles/s41416-018-0038-5 doi:10.1038/s41416-018-0038-5 doi:10.1038/s41416-018-0038-5
spellingShingle SLC3A2; Breast cancer; Prognosis
El Ansari, Rokaya
Craze, Madeleine L.
Diez-Rodriguez, Maria
Nolan, Christopher C.
Ellis, Ian O.
Rakha, Emad A.
Green, Andrew R.
The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes
title The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes
title_full The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes
title_fullStr The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes
title_full_unstemmed The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes
title_short The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes
title_sort multifunctional solute carrier 3a2 (slc3a2) confers a poor prognosis in the highly proliferative breast cancer subtypes
topic SLC3A2; Breast cancer; Prognosis
url https://eprints.nottingham.ac.uk/49376/
https://eprints.nottingham.ac.uk/49376/
https://eprints.nottingham.ac.uk/49376/