Integrative transcriptome analysis identifies genes and pathways associated with enzalutamide resistance of prostate cancer

Background: Enzalutamide, a novel androgen receptor (AR) signaling inhibitor, has been widely used to increase survival in patients with castration-resistant prostate cancer. However, resistance to enzalutamide invariably develops.Methods: To understand the underlying mechanisms of resistance to enzalutamide, we performed integrative analysis on multiple transcriptome datasets to identify those genes constantly up- or down-regulated in response to enzalutamide treatment.Results: There were 703 and 581 differentially expressed genes derived from enzalutamide-sensitive and -resistant cell lines, respectively. Functional enrichment analysis on these genes demonstrated that biological processes of cell proliferation and ubiquitin mediated proteolysis pathway are specifically disturbed in sensitive cell lines but not resistant ones. Such divergence explained why enzalutamide ineffective for resistant prostate cancer.Conclusions: Taken together, the present study revealed a set of critical genes, which can provide etiologic clues as to enzalutamide-resistant prostate cancer and guide novel therapeutic approaches.