NR2C Subfamily as a Potential Prognostic Biomarker for Hormone Receptor-Positive Breast Cancer

Abstract The overall outcome of hormone receptor-positive (HR+) breast cancer is relatively good, but it still faces the dilemmas of drug resistance and long-term recurrence. The NR2C subfamily are nuclear receptors like ER, PR and AR. However, the prognostic value and molecular mechanism of NR2Cs remain unclear. In our study, we identified the association between expression of NR2C1 or NR2C2 and survival of BRCA patients using Kaplan-Meier plotter. Next, miRNAs-NR2Cs regulatory networks were predicted by ENCORI. Furthermore, functional enrichment analysis was performed via PPI networks and KEGG pathways. Finally, CellMiner was used to obtain thecorrelation analysis of NR2Cs expression and drug sensitivity. We found that both NR2C1 and NR2C2 were significantly down-regulated in BRCA compared to normal tissues. Survival difference between high and low NR2C1 group only observed in luminal B, while high expression levels of NR2C2 were significantly associated with good prognosis in luminal A, luminal B, LAR and ER+ breast cancer. Moreover, only NR2C1-has-miR-196a network was related to the prognosis of BRCA. For NR2C2, there were thirteen miRNAs of low expression associating with good prognosis, such as hsa-miR-21, hsa-miR-656, hsa-miR-103a. The main biological functions of NR2Cs were metabolic pathways, drug metabolism, steroid hormone biosynthesis, and so on. Altogether, NR2C1 and NR2C2, especially the latter, might be novel important prognostic factors like ER/PR/AR in HR+ breast cancer.