School of Medicine, Westlake University, Hangzhou, Zhejiang Province, China; Westlake Center for Intelligent Proteomics, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang Province 310030, China; Research Center for Industries of the Future, Westlake University, 600 Dunyu Road, Hangzhou, Zhejiang 310030, China; Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, Zhejiang, China.
Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai, China; CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Cell Rep Med. 2024 Aug 20;5(8):101679. doi: 10.1016/j.xcrm.2024.101679.
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.
前列腺癌（PCa）是男性最常见的恶性肿瘤。目前，预测 PCa 结局和指导治疗的预后指标较少。在这里，我们使用数据非依赖性采集质谱（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学分析。我们鉴定了超过 10000 种蛋白质，并定义了具有显著临床和蛋白质组学差异的三种 PCa 分子亚型。我们开发了一个由 16 种蛋白质组成的小组，可有效预测 PCa 患者的生化复发（BCR），该小组通过靶向蛋白质组学在六个已发表的数据集和一个额外的 99 个活检样本队列中得到了验证。有趣的是，该 16 种蛋白质小组能够有效地预测不同国际泌尿病理学会（ISUP）分级和病理分期的 BCR，并且在 BCR 预测方面优于 D'Amico 风险分类系统。此外，敲除 NUDT5 和 SEPTIN8 这两种 16 种蛋白质小组中的成分，可显著抑制 PCa 细胞增殖、侵袭和迁移，这表明 NUDT5 和 SEPTIN8 的组合可能为 PCa 治疗提供新方法。
