Identification of molecular subtypes and a prognostic signature based on chromatin regulators related genes in prostate cancer

Abstract

The clinical and molecular phenotypes of prostate cancer (PCa) exhibit substantial heterogeneity, ranging from indolent to metastatic disease. In this study, we aimed to identify PCa subtypes and construct a gene signature that can predict the recurrence-free survival (RFS) of PCa patients based on chromatin regulators genes (CRGs). Strikingly, we identified two heterogeneous subtypes with distinct clinical and molecular characteristics. Furthermore, by performing differential analysis between the two CRGs subtypes, we successfully constructed a gene signature to predict PCa prognosis. The signature, comprising four genes (MXD3, SSTR1, AMH and PPFIA2), was utilized to classify PCa patients into two risk groups; the high-risk group was characterized by poor prognosis and more aggressive clinical features. Moreover, we investigated the immune profile, mutation landscape and molecular pathways in each of the groups. Additionally, drug-susceptibility testing was performed to explore sensitive drugs for high-risk patients. Furthermore, we found that MXD3 downregulation suppressed the proliferation of PCa cell lines in vitro. Overall, our results highlight the signature based on CRGs as a powerful tool for predicting RFS of PCa patients, as well as an indicator for personalized treatment of those patients.