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.
Cell reports. Medicine. 2024 Aug 20 [Epub]
Rui Sun, Jun A, Haolan Yu, Yan Wang, Miaoxia He, Lingling Tan, Honghan Cheng, Jili Zhang, Yingrui Wang, Xiaochen Sun, Mengge Lyu, Min Qu, Lingling Huang, Zijian Li, Wenhui Zhang, Kunpeng Ma, Zhenyang Dong, Weigang Ge, Yun Zhang, Xuan Ding, Bo Yang, Jianguo Hou, Chuanliang Xu, Linhui Wang, Yi Zhu, Tiannan Guo, Xu Gao, Chenghua Yang
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., Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai, China; Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai, China., Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai, China., Westlake Omics (Hangzhou) Biotechnology Co., Ltd., Hangzhou 310024, China., Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai, China., School of Medicine, Westlake University, Hangzhou, Zhejiang Province, China; Westlake Omics (Hangzhou) Biotechnology Co., Ltd., Hangzhou 310024, 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; Shanghai Key Laboratory of Cell Engineering, Shanghai 200433, China., 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. Electronic address: ., Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai, China; Shanghai Key Laboratory of Cell Engineering, Shanghai 200433, China. Electronic address: ., Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai, China; Shanghai Key Laboratory of Cell Engineering, Shanghai 200433, China. Electronic address: .