RESUMEN
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.
Asunto(s)
Neoplasias de la Mama/metabolismo , Receptores de Estrógenos/metabolismo , Receptor gamma X Retinoide/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Estudios de Cohortes , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Invasividad Neoplásica , Pronóstico , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptor gamma X Retinoide/biosíntesis , Receptor gamma X Retinoide/genética , Análisis de Matrices TisularesRESUMEN
PURPOSE: CD133/ prominin 1 is a cancer stem cell marker associated with cancer progression and patient outcome in a variety of solid tumours, but its role in invasive breast cancer (BC) remains obscure. The current study aims to assess the prognostic value of CD133 expression in early invasive BC. METHODS: CD133 mRNA was assessed in the METABRIC cohort and at the proteomic level using immunohistochemistry utilising a large well-characterised BC cohort. Association with clinicopathological characteristics, expression of other stem cell markers and patient outcome were evaluated. RESULTS: High expression of CD133 either in mRNA or protein levels was associated with characteristics of poor prognosis including high tumour grade, larger tumour size, high Nottingham Prognostic Index, HER2 positivity and hormonal receptor negativity (all; p < 0.001). High CD133 expression was positively associated with proliferation biomarkers including p16, Cyclin E and Ki67 (p < 0.01). Tumours expressing CD133 showed higher expression of other stem cell markers including CD24, CD44, SOX10, ALDHA3 and ITGA6. High expression of CD133 protein was associated with shorter BC-specific survival (p = 0.026). Multivariate analysis revealed that CD133 protein expression was an independent risk factor for shorter BC-specific survival (p = 0.038). CONCLUSION: This study provides evidence for the prognostic value of CD133 in invasive BC. A strong positive association of BC stem cell markers is observed at the protein level. Further studies to assess the value of stem cell markers individually or in combination in BC is warranted.