Proteomic and phosphoproteomic landscape of localized prostate cancer unveils distinct molecular subtypes and insights into precision therapeutics

• 成果类型: Article
• 署名作者: Wang, Zengming; Yu, Haolan; Bao, Wei; Qu, Min; Wang, Yan; Zhang, Liandong; Liu, Xubing; Liu, Chen; He, Miaoxia; Li, Jing; Dong, Zhenyang; Zhang, Yun; Yang, Bo; Hou, Jianguo; Xu, Chuanliang; Wang, Linhui; Li, Xin; Gao, Xu; Yang, Chenghua
• 署名单位: Naval Medical University; Chinese Academy of Sciences; Shanghai Institute of Nutrition & Health, CAS; University of Chinese Academy of Sciences, CAS; Chinese Academy of Sciences; Shanghai Institute of Nutrition & Health, CAS; University of Chinese Academy of Sciences, CAS; Naval Medical University; Shenzhen Bay Laboratory; Shanghai Jiao Tong University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12551
• DOI: 10.1073/pnas.2402741121
• 发表日期: 2024-10-01
• 关键词: proteogenomic characterization; somatic mutations; Heterogeneity; statistics; expression; EVOLUTION; networks; binding; foxa1; srsf1

摘要

Building upon our previous investigation of genomic, epigenomic, and transcriptomic profiles of prostate cancer in China, we conducted a comprehensive analysis of proteomic and phosphoproteomic profiles of 82 tumor tissues and matched adjacent normal tissues from 41 Chinese patients with localized prostate cancer. We identified three distinct proteomic subtypes with significant difference in both molecular features and clinical prognosis. Notably, these proteomic subtypes exhibited a parallel degree of heterogeneity in the phosphoproteome, featuring unique metabolism, proliferation, and immune infiltration characteristics. We further demonstrated that a combination of proteins and phosphosites serves as the most effective biomarkers in prostate cancer to predict biochemical recurrence. Through an integrated multiomics analysis, we revealed mechanistic differences underlying different proteomic subtypes and highlighted the potential significance of Serine/arginine- rich splicing factor 1 (SRSF1) phosphorylation in promoting the malignant characteristics of prostate cancer cells. Our multiomics data provide valuable resources for understanding the molecular mechanisms of prostate cancer within the Chinese population, which have the potential to inform the development of personalized treatment strategies and enhance prognostic analyses for prostate cancer patients.