前列腺癌 (PCa) 表现出显着的地理种族差异，这反映在癌症基因组和疾病进展的明显变异上。在这里，我们利用来自 125 名中国男性患者的配对肿瘤和附近组织对局部高风险 PCa 进行全面的蛋白质组学表征，主要目标是识别潜在的生物标志物、揭示关键的致癌事件并描绘预后不良的分子亚型。我们的综合分析强调了 GOLM1 作为非侵入性血清生物标志物的实用性。磷酸化蛋白质组学分析揭示了 FOXA1 上 Ser331 磷酸化在调节 FOXA1-AR 依赖性顺反子中的关键作用。值得注意的是，我们的蛋白质组分析确定了三种不同的亚型，其中代谢性免疫沙漠肿瘤 (S-III) 是一种特别具有侵袭性的亚型，与不良预后和 BCAT2 分解代谢驱动的 PCa 进展相关。总之，我们的研究提供了全面的资源，详细介绍了 PCa 分子发病机制的独特蛋白质组和磷酸化蛋白质组特征，并为诊断和治疗策略的制定提供了宝贵的见解。© 2024。作者获得 Springer Nature America 的独家许可，公司

Prostate cancer (PCa) exhibits significant geoethnic disparities as reflected by distinct variations in the cancer genome and disease progression. Here, we perform a comprehensive proteogenomic characterization of localized high-risk PCa utilizing paired tumors and nearby tissues from 125 Chinese male patients, with the primary objectives of identifying potential biomarkers, unraveling critical oncogenic events and delineating molecular subtypes with poor prognosis. Our integrated analysis highlights the utility of GOLM1 as a noninvasive serum biomarker. Phosphoproteomics analysis reveals the crucial role of Ser331 phosphorylation on FOXA1 in regulating FOXA1-AR-dependent cistrome. Notably, our proteomic profiling identifies three distinct subtypes, with metabolic immune-desert tumors (S-III) emerging as a particularly aggressive subtype linked to poor prognosis and BCAT2 catabolism-driven PCa progression. In summary, our study provides a comprehensive resource detailing the unique proteomic and phosphoproteomic characteristics of PCa molecular pathogenesis and offering valuable insights for the development of diagnostic and therapeutic strategies.© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.