Knol Jaco C, Lyu Mengge, Böttger Franziska, Nunes Monteiro Madalena, Pham Thang V, Rolfs Frank, Vallés-Martí Andrea, Schelfhorst Tim, de Goeij-de Haas Richard R, Bijnsdorp Irene V, Wang Shuaiyao, Zhang Fangfei, A Jun, Westerman Bart A, Sitek Barbara, Lehtiö Janne, Koster Jan, IJzermans Jan N M, van Laarhoven Hanneke W M, Bijlsma Maarten F, Medema Jan Paul, Henneman Alex A, Piersma Sander R, Brakenhoff Ruud H, Cloos Jacqueline, Cordo' Valentina, de Jong Daphne, Kazemier Geert, Koppers-Lalic Danijela, Labots Mariette, Le Large Tessa Y S, Martens John W M, Meijerink Jules P P, Mumtaz Madiha, Scheepbouwer Chantal, Kibbelaar Robby E, Noske David P, Steenbergen Renske D M, van Grieken Nicole C T, van Houdt Winan, Giovannetti Elisa, van Leenders Geert J L H, Jonkers Jos, Liu Tong, Yan Meisi, Zhan Xiaolu, Guo Tiannan, Jimenez Connie R
Amsterdam UMC, location Vrije Universiteit Amsterdam, Department of Medical Oncology, OncoProteomics Laboratory, De Boelelaan 1117, Amsterdam, the Netherlands; Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, the Netherlands.
School of Medicine, Westlake University, Hangzhou, Zhejiang, China; Westlake Center for Intelligent Proteomics, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China.
Cancer Cell. 2025 May 27. doi: 10.1016/j.ccell.2025.05.003.
Most cancer proteomics studies to date have focused on a single cancer type. We report The Pan-Cancer Proteome Atlas (TPCPA) based on data-independent acquisition mass spectrometry, to better understand cancer biology and identify therapeutic targets and biomarkers. TPCPA includes 9,670 proteins derived from 999 primary tumors representing 22 cancer types. We describe pan-cancer and cancer type-enriched proteins with extensive external annotation, prioritizing candidate drug targets and biomarkers. Relevant for proteolysis-targeting chimeras, we identify E3-ubiquitin ligases highly expressed in specific tumor types, including HERC5 (esophageal cancer) and RNF5 (liver cancer). Co-expression analysis reveals 13 modules, including unexpected hub proteins as potential drug targets (e.g., GFPT1, LRPPRC, PINK1, DOCK2, and PTPN6). Analysis of 195 colorectal cancers identifies protein markers for RNA-based consensus molecular subtypes (CMSs) and two immune subtypes with prognostic value. We report a cancer type classifier for identification of cancers of unknown primary origin. All TPCPA data can be queried in a dedicated web resource.
迄今为止，大多数癌症蛋白质组学研究都集中在单一癌症类型上。我们报告了基于数据非依赖采集质谱技术的泛癌蛋白质组图谱（TPCPA），以更好地理解癌症生物学并识别治疗靶点和生物标志物。TPCPA包含来自代表22种癌症类型的999个原发性肿瘤的9670种蛋白质。我们用广泛的外部注释描述泛癌和癌症类型富集的蛋白质，对候选药物靶点和生物标志物进行优先级排序。对于靶向蛋白水解嵌合体而言，我们鉴定出在特定肿瘤类型中高表达的E3泛素连接酶，包括HERC5（食管癌）和RNF5（肝癌）。共表达分析揭示了13个模块，包括作为潜在药物靶点的意外中心蛋白（例如，GFPT1、LRPPRC、PINK1、DOCK2和PTPN6）。对195例结直肠癌的分析确定了基于RNA的共识分子亚型（CMS）和两种具有预后价值的免疫亚型的蛋白质标志物。我们报告了一种用于识别原发性不明癌症的癌症类型分类器。所有TPCPA数据都可以在一个专门的网络资源中查询。
