title: The Major Prognostic Features of Nuclear Receptor NR5A2 in Infiltrating Ductal Breast Carcinomas.
abstract: Background. Gene expression profiles of 181 breast cancer samples were analyzed to identify prognostic features of nuclear receptors NR5A1 and NR5A2 based 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. NR5A2 expression is a negative factor in breast cancer prognosis in both ER(-) and ER(-)/ER(+) mixed cohorts. The clinical and cohort significance of NR5A2-mediated transcriptional activities indicates that it may have a significant role in attenuating grade development and cancer related signal transduction pathways. NR5A2 signature that conditions poor prognosis was identified based upon results from 15 distinct probes. Alternatively, the expression of NR5A1 predicts favorable prognosis when concurrent NR5A2 expression is low. A favorable signature of eight transcription factors mediated by NR5A1 was also identified. Conclusions. Correlation of poor prognosis and NR5A2 activity is identified by NR5A2-mediated 15-gene signature. NR5A2 may 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 of NR5A1 is predicted by NR5A1-mediated 8-gene signature.
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Li-Yun
authors.initials: LY
authors.lastname: Chang
authors.affiliation: Biometry Division, Department of Agronomy, National Taiwan University, Taipei 106, Taiwan.
authors.forename: Li-Yu D
authors.initials: LY
authors.lastname: Liu
authors.affiliation: Department of Molecular Biology, University of Wyoming, Laramie, WY 82071, USA.
authors.forename: Don A
authors.initials: DA
authors.lastname: Roth
authors.affiliation: Department of Surgery, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Wen-Hung
authors.initials: WH
authors.lastname: Kuo
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Hsiao-Lin
authors.initials: HL
authors.lastname: Hwa
authors.affiliation: Department of Surgery, College of Medicine, National Taiwan University, Taipei 100, Taiwan ; Cheng Ching General Hospital, Taichung 400, Taiwan.
authors.forename: King-Jen
authors.initials: KJ
authors.lastname: Chang
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei 100, Taiwan ; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Fon-Jou
authors.initials: FJ
authors.lastname: Hsieh