Proteomic-coupled-network analysis of T877A-androgen receptor interactomes can predict clinical prostate cancer outcomes between White (non-Hispanic) and African-American groups.

摘要: The androgen receptor (AR) remains an important contributor to the neoplastic evolution of prostate cancer (CaP). CaP progression is linked several somatic AR mutational changes that endow upon dramatic gain-of-function properties. One most common mutations identified Thr877-to-Ala (T877A), located in ligand-binding domain, results a capable promiscuous binding and activation by variety steroid hormones ligands including estrogens, progestins, glucocorticoids, anti-androgens. In attempt further define mutated properties, as consequence its ligand binding, we undertook proteomic/network analysis approach characterize protein interactome mutant T877A-AR LNCaP cells under eight different ligand-specific treatments (dihydrotestosterone, mibolerone, R1881, testosterone, estradiol, progesterone, dexamethasone, cyproterone acetate). extending our multi-ligand complexes observed significant enrichment specific between normal primary prostatic tumors, which were furthermore correlated with known clinical outcomes. Further certain showed population preferences distinguishing disease white (non-Hispanic) vs. African-American males. Moreover, these cancer-related AR-protein demonstrated predictive survival outcomes CaP, not for breast, lung, lymphoma or medulloblastoma cancers. Our study, coupling data generated proteomics network samples, has helped real novel biological pathways complicated complex systems.