Retinoid X receptor gamma (RXRG) is an independent prognostic biomarker in ER-positive invasive breast cancer

Joseph, Chitra; Al-Izzi, Sara; Alsaleem, Mansour; Kurozumi, Sasagu; Toss, Michael; Arshad, Maariya; Goh, Fang Qin; Alshankyty, Ibraheem M; Ali, Simak; Ellis, Ian O; Mongan, Nigel P; Green, Andrew R; Rakha, Emad A

Abstract

© 2019, The Author(s), under exclusive licence to Cancer Research UK. Background: Retinoid X Receptor Gamma (RXRG) is a member of the nuclear receptor superfamily and plays a role in tumour suppression. This study aims to explore the prognostic significance of RXRG in breast cancer. Methods: Primary breast cancer tissue microarrays (n = 923) were immuno-stained for RXRG protein and correlated with clinicopathological features, and patient outcome. Results: Nuclear RXRG expression was significantly associated with smaller tumour size (p = 0.036), lower grade (p < 0.001), lobular histology (p = 0.016), lower Nottingham Prognostic Index (p = 0.04) and longer breast cancer-specific survival (p < 0.001), and longer time to distant metastasis (p = 0.002). RXRG expression showed positive association with oestrogen receptor (ER)-related biomarkers: GATA3, FOXA1, STAT3 and MED7 (all p < 0.001) and a negative correlation with the Ki67 proliferation marker. Multivariate analysis demonstrated RXRG protein as an independent predictor of longer breast cancer-specific survival and distant metastasis-free survival. In the external validation cohorts, RXRG expression was associated with improved patients’ outcome (p = 0.025). In ER-positive tumours, high expression of RXRG was associated with better patient outcome regardless of adjuvant systemic therapy. ER signalling pathway was the top predicted master regulator of RXRG protein expression (p = 0.005). Conclusion: This study provides evidence for the prognostic value of RXRG in breast cancer particularly the ER-positive tumours.

Citation

Joseph, C., Al-Izzi, S., Alsaleem, M., Kurozumi, S., Toss, M., Arshad, M., …Rakha, E. A. (2019). Retinoid X receptor gamma (RXRG) is an independent prognostic biomarker in ER-positive invasive breast cancer. British Journal of Cancer, 121(9), 776-785. https://doi.org/10.1038/s41416-019-0589-0

• Journal Article Type: Article
• Acceptance Date: Aug 9, 2019
• Online Publication Date: Sep 27, 2019
• Publication Date: 2019-10
• Deposit Date: Aug 21, 2019
• Publicly Available Date: Mar 28, 2020
• Journal: British Journal of Cancer
• Print ISSN: 0007-0920
• Electronic ISSN: 1532-1827
• Publisher: Cancer Research UK
• Peer Reviewed: Peer Reviewed
• Volume: 121
• Issue: 9
• Pages: 776-785
• DOI: https://doi.org/10.1038/s41416-019-0589-0
• Keywords: Nuclear receptor; Retinoid X Receptor Gamma (RXRG; RXR); ER positive IBC
• Public URL: https://nottingham-repository.worktribe.com/output/2454029
• Contract Date: Aug 21, 2019