Prostate adenocarcinoma (PRAD) represents the most common male carcinoma in developed countries, its high relapse risk contributes to the second-leading cause of cancer-related deaths. Therefore, it is required to develop an effective signature for predicting the relapse risk of PRAD. To identify a circadian rhythm- (CR-) related predictive signature, we analyzed RNA-seq data of patients with prostate adenocarcinoma (PRAD) from the TCGA and GEO cohort. Seven circadian rhythm- (CR-) related genes (FBXL22, MTA1, TP53, RORC, DRD4, PPARGC1A, ZFHX3) were eventually identified to develop a CR-related signature. AUCs for 3-year overall survival were 0.852, 0.856 and 0.944 in the training set, validation set and an external independent test set (GSE70768), respectively. Kaplan-Meier curve analysis showed that the high-risk group has a reduced relapse-free survival (RFS) than the low-risk group in the training set, validation set, and test set, respectively (P < 0.05). We constructed a prognostic nomogram combining the CR-related signature with T staging to precisely estimate relapse risk of PRAD patients. Finally, we observed that the CR-related gene signature was associated with tumor mutation burden, multiple immune checkpoint molecules and microsatellite instability, and thus could predict response to immune checkpoint inhibitors in PRAD. Conclusively, we developed a circadian rhythm-related gene signature for predicting RFS and immunotherapy efficacy in prostate adenocarcinoma.

中文翻译：

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用于预测前列腺癌复发风险和免疫治疗效果的昼夜节律相关基因特征

前列腺癌 (PRAD) 是发达国家中最常见的男性癌症，其高复发风险是癌症相关死亡的第二大原因。因此，需要开发一种有效的特征来预测 PRAD 的复发风险。为了确定与昼夜节律 (CR-) 相关的预测特征，我们分析了来自 TCGA 和 GEO 队列的前列腺腺癌 (PRAD) 患者的 RNA-seq 数据。七个昼夜节律 - (CR-) 相关基因 ( FBXL22 , MTA1 , TP53 , RORC , DRD4 , PPARGC1A , ZFHX3) 最终确定要开发与 CR 相关的签名。在训练集、验证集和外部独立测试集 (GSE70768) 中，3 年总生存期的 AUC 分别为 0.852、0.856 和 0.944。Kaplan-Meier曲线分析显示，高危组在训练集、验证集和测试集上分别比低危组的无复发生存率（RFS）降低（P< 0.05)。我们构建了一个预后列线图，将 CR 相关特征与 T 分期相结合，以精确估计 PRAD 患者的复发风险。最后，我们观察到 CR 相关基因特征与肿瘤突变负荷、多个免疫检查点分子和微卫星不稳定性相关，因此可以预测 PRAD 中对免疫检查点抑制剂的反应。最后，我们开发了一种与昼夜节律相关的基因标记，用于预测前列腺癌的 RFS 和免疫治疗效果。