Ma Hangbin, Zhou Cheng, Ge Jianchao, Yu Wandong, Zhou Yinghao, Wang Pengyu, Zhang Xuehu, Zhang Jun, Shi Guowei
Department of Urology, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China.
Front Genet. 2023 Jan 10;13:1110723. doi: 10.3389/fgene.2022.1110723. eCollection 2022.
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 . 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.
前列腺癌（PCa）的临床和分子表型表现出显著的异质性，从惰性疾病到转移性疾病不等。在本研究中，我们旨在识别PCa亚型，并基于染色质调节基因（CRGs）构建一个能够预测PCa患者无复发生存期（RFS）的基因特征。令人惊讶的是，我们识别出了两种具有不同临床和分子特征的异质性亚型。此外，通过对两种CRGs亚型进行差异分析，我们成功构建了一个预测PCa预后的基因特征。该特征由四个基因（MXD3、SSTR1、AMH和PPFIA2）组成，用于将PCa患者分为两个风险组；高风险组的特点是预后较差且临床特征更具侵袭性。此外，我们研究了每组的免疫特征、突变图谱和分子途径。另外，进行了药物敏感性测试以探索高风险患者的敏感药物。此外，我们发现MXD3下调抑制了PCa细胞系的增殖。总体而言，我们的结果强调基于CRGs的特征是预测PCa患者RFS的有力工具，也是这些患者个性化治疗的指标。
