Roshni Patel
ATF4 as a Prognostic Marker and Modulator of Glutamine Metabolism in Estrogen Receptor Positive Breast Cancer
Patel, Roshni; Alfarsi, Lutfi H.; El-Ansari, Rokaya; Masisi, Brendah K.; Erkan, Busra; Fakroun, Ali; Ellis, Ian O.; Rakha, Emad A.; Green, Andrew R.
Authors
Lutfi H. Alfarsi
Rokaya El-Ansari
Brendah K. Masisi
Busra Erkan
Ali Fakroun
Ian O. Ellis
EMAD RAKHA Emad.Rakha@nottingham.ac.uk
Professor of Breast Cancer Pathology
ANDREW GREEN ANDREW.GREEN@NOTTINGHAM.AC.UK
Associate Professor
Abstract
Purpose: ATF4, a stress-responsive transcription factor that upregulates adaptive genes, is a potential prognostic marker and modulator of glutamine metabolism in breast cancer. However, its exact role remains to be elucidated.
Methods: ATF4 expression was evaluated at genomic and transcriptomic levels using METABRIC (n=1980), GeneMiner (n=4712) and KM-Plotter datasets. Proteomic expression was assessed via immunohistochemistry (n=2225) in the Nottingham Primary Breast Cancer Series. ATF4 genomic copy number (CN) variation and mRNA/protein in association with clinicopathological parameters, amino acid transporters (AATs), and patient outcome was investigated.
Results:
Genomic, transcriptomic, and proteomic overexpression of ATF4 was associated with more aggressive ER-negative tumours. ATF4 mRNA and protein expression were significantly associated with increased expression of glutamine related AATs including SLC1A5 (p<0.01) and SLC7A11 (p<0.02). High ATF4 and SLC1A5 protein expression was significantly associated with shorter breast cancer-specific survival (p<0.01), especially in ER+ tumours (p<0.01), while high ATF4 and SLC7A11 protein expression was associated with shorter survival (p<0.01).
Conclusion: These findings suggest a complex interplay between ATF4 and AATs in breast cancer biology and underscore the potential role for ATF4 as a prognostic marker in ER+ breast cancer, offering a unique opportunity for risk stratification and personalised treatment strategies.
Citation
Patel, R., Alfarsi, L. H., El-Ansari, R., Masisi, B. K., Erkan, B., Fakroun, A., …Green, A. R. (in press). ATF4 as a Prognostic Marker and Modulator of Glutamine Metabolism in Estrogen Receptor Positive Breast Cancer. Pathobiology, https://doi.org/10.1159/000539564
Journal Article Type | Article |
---|---|
Acceptance Date | May 25, 2024 |
Online Publication Date | Jun 11, 2024 |
Deposit Date | May 28, 2024 |
Publicly Available Date | Jun 11, 2024 |
Journal | Pathobiology |
Print ISSN | 1015-2008 |
Electronic ISSN | 1423-0291 |
Publisher | Karger Publishers |
Peer Reviewed | Peer Reviewed |
DOI | https://doi.org/10.1159/000539564 |
Keywords | activating-transcription factor 4; breast cancer; glutamine metabolism; amino-acid transporters 2 |
Public URL | https://nottingham-repository.worktribe.com/output/35429989 |
Publisher URL | https://karger.com/pat/article/doi/10.1159/000539564/909095/ATF4-as-a-Prognostic-Marker-and-Modulator-of |
Files
ATF4 V20 Manuscript
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Licence
https://creativecommons.org/licenses/by/4.0/
Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/
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