Retinoid X receptor gamma (RXRG) is an independent prognostic biomarker in ER-positive invasive breast cancer.
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Published version
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2019-09-27
Date Acceptance
2019-09-05
Citation
British Journal of Cancer, 2019, 121, pp.776-785
ISSN
0007-0920
Publisher
Springer Nature [academic journals on nature.com]
Start Page
776
End Page
785
Journal / Book Title
British Journal of Cancer
Volume
121
Copyright Statement
© The Author(s), under exclusive licence to Cancer Research UK 2019. This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/31558802
PII: 10.1038/s41416-019-0589-0
Subjects
1112 Oncology and Carcinogenesis
Oncology & Carcinogenesis
Publication Status
Published
Coverage Spatial
England
Article Number
221
Date Publish Online
2019-09-27