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

IF 48.8 1区医学 Q1 CELL BIOLOGY

Cancer Cell Pub Date : 2025-05-29 DOI:10.1016/j.ccell.2025.05.003

Jaco C. Knol, Mengge Lyu, Franziska Böttger, 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 Lehtiö, Jan Koster, Jan N.M. IJzermans, Hanneke W.M. van Laarhoven, Maarten F. Bijlsma, Connie R. Jimenez

{"title":"The pan-cancer proteome atlas, a mass spectrometry-based landscape for discovering tumor biology, biomarkers, and therapeutic targets","authors":"Jaco C. Knol, Mengge Lyu, Franziska Böttger, 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 Lehtiö, Jan Koster, Jan N.M. IJzermans, Hanneke W.M. van Laarhoven, Maarten F. Bijlsma, Connie R. Jimenez","doi":"10.1016/j.ccell.2025.05.003","DOIUrl":null,"url":null,"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.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"31 1","pages":""},"PeriodicalIF":48.8000,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Cell","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ccell.2025.05.003","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

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.

Abstract Image

查看原文本刊更多论文

泛癌症蛋白质组图谱，发现肿瘤生物学，生物标志物和治疗靶点的质谱为基础的景观

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。我们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。我们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，我们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。我们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数据都可以在专门的web资源中查询。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cancer Cell 医学-肿瘤学

CiteScore

55.20

自引率

1.20%

发文量

179

审稿时长

4-8 weeks

期刊介绍： Cancer Cell is a journal that focuses on promoting major advances in cancer research and oncology. The primary criteria for considering manuscripts are as follows: Major advances: Manuscripts should provide significant advancements in answering important questions related to naturally occurring cancers. Translational research: The journal welcomes translational research, which involves the application of basic scientific findings to human health and clinical practice. Clinical investigations: Cancer Cell is interested in publishing clinical investigations that contribute to establishing new paradigms in the treatment, diagnosis, or prevention of cancers. Insights into cancer biology: The journal values clinical investigations that provide important insights into cancer biology beyond what has been revealed by preclinical studies. Mechanism-based proof-of-principle studies: Cancer Cell encourages the publication of mechanism-based proof-of-principle clinical studies, which demonstrate the feasibility of a specific therapeutic approach or diagnostic test.