SP5.2 High Nuclear Receptor 4A1 (NR4A1) expression is associated with poor prognosis in breast cancer patients
Stacey Jones- Surgery
Abstract
Aim
To evaluate the relevance of NR4A1 expression with respect to clinical prognostic markers and outcomes in a breast cancer cohort, as well as the METABRIC dataset.
Methods
Breast cancer tissue was obtained from a tissue microarray comprising all tumour subtypes, with common factor of use of adjuvant chemotherapy (n=305). Expression of NR4A1 was determined by immunohistochemistry. METABRIC data were accessed via cBioPortal. Records with suitable NR4A1 expression data and clinical data of relevance were obtained (n=1886). For both cohorts, cases were then dichotomised into high or low NR4A1 expression by performing receiver operator curve analyses, and relationships between expression and survival were tested.
Results
Kaplan-Meier survival analyses showed that high NR4A1 nuclear protein expression was associated with a poorer disease-free survival (DFS) and disease-specific survival (DSS), by means of 487 days, p=0.005; 621 days, p=0.001 respectively in the whole cohort. A sub-analysis of triple negative and ER-negative breast cancers also showed that high NR4A1 nuclear protein expression was associated with both a shorter DFS, by 1452 days, p=0.002; 1141 days, p=0.006 respectively and DSS, by 1603 days, p=0.001; 1187 days, p=0.001 respectively. Analyses of the METABRIC dataset demonstrated no significant influence of NR4A1 mRNA expression on DFS (p=0.978) or DSS (p=0.288) in the whole cohort, or the molecular subgroups, or depending on chemotherapy use.
Conclusion
High nuclear NR4A1 expression correlates with decreased DFS and DSS after chemotherapy in breast cancer and these findings suggest that NR4A1 could act as a potential target for inhibitor drugs in breast cancer.