在临床前模型中，异常的 Wnt 信号传导与前列腺癌肿瘤发生和转移有关，但 Wnt 信号传导基因的遗传改变对晚期前列腺癌男性的影响尚不清楚。我们利用前列腺癌精准医学多机构协作努力 (PROMISE) 临床-用于回顾性分析的基因组数据库。 CTNNB1或RSPO2激活突变或APC、RNF43或ZNRF3失活突变的患者被定义为Wnt改变，而缺乏此类改变的患者被定义为Wnt非改变。我们根据 Wnt 改变状态比较了患者特征和临床结果以及同时发生的遗传改变。在纳入的 1498 名患者中，193 名 (12.9%) 发生 Wnt 改变。与初次诊断时 Wnt 无改变的患者相比，这些男性的肝和肺转移患病率显着增加了 2 倍（4.66% vs 2.15%；6.22% vs 3.07%），首次诊断为转移性疾病（ 10.88% 对 5.29%；13.99% 对 6.21%），以及 CRPC 发展（11.40% 对 6.36%；12.95% 对 5.29%）。 Wnt 改变与 RB1 (10.4% vs 6.2%)、AR (38.9% vs 25.7%)、SPOP (13.5% vs 4.1%)、FOXA1 (6.7% vs 2.8%) 和 PIK3CA 中更多同时发生的改变相关。 10.9% 对比 5.1%）。我们发现 Wnt 组之间从初始诊断、首次转移性疾病、CRPC 诊断或针对 mCRPC 的 AR 抑制来看，总体生存率或其他临床结果没有显着差异。Wnt 改变的前列腺癌患者内脏转移的发生率较高，并且富含 RB1、AR、SPOP、FOXA1 和 PIK3CA 改变。尽管存在这些关联，Wnt 改变与晚期前列腺癌男性较差的生存或治疗结果无关。© 2024。作者，获得 Springer Nature Limited 的独家许可。

Aberrant Wnt signaling has been implicated in prostate cancer tumorigenesis and metastasis in preclinical models but the impact of genetic alterations in Wnt signaling genes in men with advanced prostate cancer is unknown.We utilized the Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) clinical-genomic database for this retrospective analysis. Patients with activating mutations in CTNNB1 or RSPO2 or inactivating mutations in APC, RNF43, or ZNRF3 were defined as Wnt-altered, while those lacking such alterations were defined as Wnt non-altered. We compared patient characteristics and clinical outcomes as well as co-occurring genetic alterations according to Wnt alteration status.Of the 1498 patients included, 193 (12.9%) were Wnt-altered. These men had a statistically significant 2-fold increased prevalence of liver and lung metastases as compared with Wnt non-altered patients at the time of initial diagnosis, (4.66% v 2.15% ; 6.22% v 3.07%), first metastatic disease diagnosis (10.88% v 5.29%; 13.99% v 6.21%), and CRPC development (11.40% v 6.36%; 12.95% v 5.29%). Wnt alterations were associated with more co-occurring alterations in RB1 (10.4% v 6.2%), AR (38.9% vs 25.7%), SPOP (13.5% vs 4.1%), FOXA1 (6.7% vs 2.8%), and PIK3CA (10.9% vs 5.1%). We found no significant differences in overall survival or other clinical outcomes from initial diagnosis, first metastatic disease, diagnosis of CRPC, or with AR inhibition for mCRPC between the Wnt groups.Wnt-altered patients with prostate cancer have a higher prevalence of visceral metastases and are enriched in RB1, AR, SPOP, FOXA1, and PIK3CA alterations. Despite these associations, Wnt alterations were not associated with worse survival or treatment outcomes in men with advanced prostate cancer.© 2024. The Author(s), under exclusive licence to Springer Nature Limited.