近日，荷兰阿姆斯特丹癌症中心教授Connie R. Jimenez团队的研究开发出了泛癌蛋白质组图谱：基于质谱的肿瘤生物学、生物标志物与治疗靶点发现平台。相关论文于2025年5月29日发表在《癌细胞》杂志上。

研究小组报告了基于数据独立获取质谱的泛癌症蛋白质组图谱（TPCPA），以更好地了解癌症生物学并确定治疗靶点和生物标志物。TPCPA包含9670个蛋白质，这些蛋白质来自代表22种癌症类型的999个原发肿瘤。课题组人员用广泛的外部注释描述泛癌症和癌症类型富集的蛋白质，优先考虑候选药物靶点和生物标志物。与蛋白水解靶向嵌合体相关，小组发现了在特定肿瘤类型中高度表达的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，包括意想不到的枢纽蛋白作为潜在的药物靶点（例如，GFPT1， LRPPRC, PINK1， DOCK2和PTPN6）。对195例结直肠癌的分析发现了基于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记物。课题组人员报告了一种癌症类型分类器，用于鉴定未知原发癌症。所有TPCPA数据都可以在专用的web抗性中查询。

据悉，迄今为止，大多数癌症蛋白质组学研究都集中在一种癌症类型上。

附：英文原文

Title: The pan-cancer proteome atlas, a mass spectrometry-based landscape for discovering tumor biology, biomarkers, and therapeutic targets

Author: Jaco C. Knol, Mengge Lyu, Franziska Bttger, Madalena Nunes Monteiro, Thang V. Pham, Frank Rolfs, Andrea Vallés-Martí, Tim Schelfhorst, Richard R. de Goeij-de Haas, Irene V. Bijnsdorp, Shuaiyao Wang, Fangfei Zhang, Jun A, Bart A. Westerman, Barbara Sitek, Janne Lehti, Jan Koster, Jan N.M. IJzermans, Hanneke W.M. van Laarhoven, Maarten F. Bijlsma, Jan Paul Medema, Alex A. Henneman, Sander R. Piersma, Ruud H. Brakenhoff, Jacqueline Cloos, Valentina Cordo, Daphne de Jong, Geert Kazemier, Danijela Koppers-Lalic, Mariette Labots, Tessa Y.S. Le Large, John W.M. Martens, Jules P.P. Meijerink, Madiha Mumtaz, Chantal Scheepbouwer, Robby E. Kibbelaar, David P. Noske, Renske D.M. Steenbergen, Nicole C.T. van Grieken, Winan van Houdt, Elisa Giovannetti, Geert J.L.H. van Leenders, Jos Jonkers, Tong Liu, Meisi Yan, Xiaolu Zhan, Tiannan Guo, Connie R. Jimenez

Issue&Volume: 2025-05-29

Abstract: 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.

DOI: 10.1016/j.ccell.2025.05.003

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00212-0