前列腺癌（PCa）是男性最常见的恶性肿瘤。目前，用于预测PCa结局和指导治疗的预后指标很少。在这里，我们使用数据独立采集质谱 (DIA-MS) 对来自 306 名中国 PCa 患者的 918 份组织标本进行了全面的蛋白质组分析。我们鉴定了超过 10,000 种蛋白质，并定义了三种具有显着临床和蛋白质组差异的 PCa 分子亚型。我们开发了一个 16 蛋白组，可以有效预测 PCa 患者的生化复发 (BCR)，并通过目标蛋白质组学在六个已发表的数据集和另外一个 99 个活检样本队列中得到验证。有趣的是，这个 16 蛋白面板可以有效预测不同国际泌尿病理学会 (ISUP) 分级和病理阶段的 BCR，并且在 BCR 预测方面优于 D'Amico 风险分类系统。此外，16蛋白组中的两个成分NUDT5和SEPTIN8的双敲除显着抑制PCa细胞的增殖、侵袭和迁移，表明NUDT5和SEPTIN8的组合可能为PCa治疗提供新方法。版权所有©2024作者。由爱思唯尔公司出版。保留所有权利。

Prostate cancer (PCa) is the most common malignant tumor in men. Currently, there are few prognosis indicators for predicting PCa outcomes and guiding treatments. Here, we perform comprehensive proteomic profiling of 918 tissue specimens from 306 Chinese patients with PCa using data-independent acquisition mass spectrometry (DIA-MS). We identify over 10,000 proteins and define three molecular subtypes of PCa with significant clinical and proteomic differences. We develop a 16-protein panel that effectively predicts biochemical recurrence (BCR) for patients with PCa, which is validated in six published datasets and one additional 99-biopsy-sample cohort by targeted proteomics. Interestingly, this 16-protein panel effectively predicts BCR across different International Society of Urological Pathology (ISUP) grades and pathological stages and outperforms the D'Amico risk classification system in BCR prediction. Furthermore, double knockout of NUDT5 and SEPTIN8, two components from the 16-protein panel, significantly suppresses the PCa cells to proliferate, invade, and migrate, suggesting the combination of NUDT5 and SEPTIN8 may provide new approaches for PCa treatment.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.