Diagnostic and prognostic role of NR3C4 in breast cancer through a genomic network understanding.

The androgen receptor (AR, NR3C4) is believed to participate in the development of breast cancer, but its molecular mechanism and role in prognosis is still controversial and opaque. This study aimed to explore the expression, associations with clinicopathologic features and underlying molecular mechanisms of AR in breast cancer. The present study investigated invasive breast carcinoma through comprehensive bioinformatics. The expression and mutation rate of AR in breast cancer was obtained from the TCGA database. Training survival prediction analysis was applied to the data extracted from the KM plotter database. The prediction of the survival cohort was validated using the bcGenExMiner database in breast cancer molecular subgroups. Represented immunohistochemical images of AR and its related expression with the molecular subtype status were generated. The underlying molecular mechanism for AR in breast cancer was analyzed with the GEO dataset and Gene Ontology. A protein-to-protein interaction network and core pathways were constructed to show the protein functions with AR. Our results show that AR expression was significantly higher in cancerous tissue than in normal breast tissue and differentially expressed in the clinical stages. AR would also generally be considered as a favorable prognostic biomarker when including the major molecular subtypes of breast cancer. AR IHC staining could be easily used in clinical applications. The major molecular functions for AR were regulating the cell cycle checkpoints and chromatin remodeling. Our investigation showed that AR expression level could be used as a favorable and independent prognostic prediction factor for the disease-free survival time in breast cancer, especially for the ER-positive subgroup. However, AR was not a sensitive prognostic biomarker for the prediction of overall survival time or for the PR and TBC subgroups. In terms of the underlying molecular mechanism, AR may mainly participate in the cell cycle checkpoints related to the G1/S transition of the mitotic cell cycle to control the subdivision of the epithelial terminal unit and chromatin remodeling in breast cancer.