Low expression of G protein-coupled oestrogen receptor 1 (GPER) is associated with adverse survival of breast cancer patients
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Stewart G. Martin1,4, Marie N. Lebot1,4, Bhudsaban Sukkarn1,4, Graham Ball2, Andrew R. Green3,4, Emad A. Rakha3,4, Ian O. Ellis3,4 and Sarah J. Storr1,4
1Translational and Radiation Biology Research Group, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham City Hospital, Nottingham, NG5 1PB, UK
2John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Campus, Nottingham, NG1 4BU, UK
3Academic Pathology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham City Hospital, Nottingham, NG5 1PB, UK
4Nottingham Breast Cancer Research Centre, University of Nottingham, Nottingham City Hospital, Nottingham, NG5 1PB, UK
Sarah J. Storr, email: [email protected]
Keywords: GPER; breast cancer; ER; oestrogen; prognosis
Received: November 30, 2017 Accepted: April 28, 2018 Published: May 25, 2018
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.
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