The Major Prognostic Features of Nuclear ReceptorNR5A2in Infiltrating Ductal Breast Carcinomas

Abstract

Background. Gene expression profiles of 181 breast cancer samples were analyzed to identify prognostic features of nuclear receptorsNR5A1andNR5A2based upon their associated transcriptional networks.Methods. A supervised network analysis approach was used to build the NR5A-mediated transcriptional regulatory network. Other bioinformatic tools and statistical methods were utilized to confirm and extend results from the network analysis methodology.Results.NR5A2expression is a negative factor in breast cancer prognosis in both ER(−) and ER(−)/ER(+) mixed cohorts. The clinical and cohort significance ofNR5A2-mediated transcriptional activities indicates that it may have a significant role in attenuating grade development and cancer related signal transduction pathways.NR5A2signature that conditions poor prognosis was identified based upon results from 15 distinct probes. Alternatively, the expression ofNR5A1predicts favorable prognosis when concurrentNR5A2expression is low. A favorable signature of eight transcription factors mediated byNR5A1was also identified.Conclusions. Correlation of poor prognosis andNR5A2activity is identified byNR5A2-mediated 15-gene signature.NR5A2may be a potential drug target for treating a subset of breast cancer tumors across breast cancer subtypes, especially ER(−) breast tumors. The favorable prognostic feature ofNR5A1is predicted byNR5A1-mediated 8-gene signature.