Low expression of G protein-coupled oestrogen receptor 1 (GPER) is associated with adverse survival of breast cancer patients

Martin, Stewart G.; Lebot, Marie N.; Sukkarn, Bhudsaban; Ball, Graham; Green, Andrew R.; Rakha, Emad A.; Ellis, Ian O.; Storr, Sarah J.

Abstract

G protein-coupled oestrogen receptor 1 (GPER), also called G protein-coupled receptor 30 (GPR30), is attracting considerable attention for its potential role in breast cancer development and progression. Activation by oestrogen (17β-oestradiol; E2) initiates short term, non-genomic, signalling events both in vitro and in vivo. Published literature on the prognostic value of GPER protein expression in breast cancer indicates that further assessment is warranted. We show, using immunohistochemistry on a large cohort of primary invasive breast cancer patients (n=1245), that low protein expression of GPER is not only significantly associated with clinicopathological and molecular features of aggressive behaviour but also significantly associated with adverse survival of breast cancer patients. Furthermore, assessment of GPER mRNA levels in the METABRIC cohort (n=1980) demonstrates that low GPER mRNA expression is significantly associated with adverse survival of breast cancer patients. Using artificial neural networks, genes associated with GPER mRNA expression were identified; these included notch-4 and jagged-1. These results support the prognostic value for determination of GPER expression in breast cancer.

Citation

Martin, S. G., Lebot, M. N., Sukkarn, B., Ball, G., Green, A. R., Rakha, E. A., Ellis, I. O., & Storr, S. J. (2018). Low expression of G protein-coupled oestrogen receptor 1 (GPER) is associated with adverse survival of breast cancer patients. Oncotarget, 9(40), 25946-25956. https://doi.org/10.18632/oncotarget.25408

• Journal Article Type: Article
• Acceptance Date: Apr 28, 2018
• Online Publication Date: May 8, 2018
• Publication Date: May 25, 2018
• Deposit Date: Sep 5, 2018
• Publicly Available Date: Sep 5, 2018
• Journal: Oncotarget
• Publisher: Impact Journals
• Peer Reviewed: Peer Reviewed
• Volume: 9
• Issue: 40
• Pages: 25946-25956
• DOI: https://doi.org/10.18632/oncotarget.25408
• Public URL: https://nottingham-repository.worktribe.com/output/1061127
• Publisher URL: http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=25408&path[]=79578
• Contract Date: Sep 5, 2018