The pan-cancer proteome atlas, a mass spectrometry-based landscape for discovering tumor biology, biomarkers, and therapeutic targets
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.
Authors
- Maarten F. Bijlsma (ORCID: https://orcid.org/0000-0001-6627-3229)
- Tiannan Guo (ORCID: https://orcid.org/0000-0003-3869-7651)
- Thang V. Pham (ORCID: https://orcid.org/0000-0003-0333-2492)
- Daphne de Jong (ORCID: https://orcid.org/0000-0002-9725-4060)
- Danijela Koppers‐Lalic (ORCID: https://orcid.org/0000-0002-1050-7521)
- Mariëtte Labots (ORCID: https://orcid.org/0000-0002-7095-1771)
- Meisi Yan
- Jun Arita
- Franziska Böttger (ORCID: https://orcid.org/0000-0001-8364-4087)
- Andrea Vallés‐Martí (ORCID: https://orcid.org/0000-0002-6557-0130)
- Tessa Y. S. Le Large (ORCID: https://orcid.org/0000-0002-4273-7217)
- Madiha Mumtaz
- Jan Paul Medema (ORCID: https://orcid.org/0000-0003-3045-2924)
- Tim Schelfhorst (ORCID: https://orcid.org/0000-0003-3444-0971)
- Elisa Giovannetti (ORCID: https://orcid.org/0000-0002-7565-7504)
- Alex A. Henneman (ORCID: https://orcid.org/0000-0002-3746-4410)
- Irene V. Bijnsdorp (ORCID: https://orcid.org/0000-0002-4261-3820)
- Shuaiyao Wang
- Janne Lehtiö (ORCID: https://orcid.org/0000-0002-8100-9562)
- Jules P.P. Meijerink (ORCID: https://orcid.org/0000-0002-6860-798X)
- David P. Noske (ORCID: https://orcid.org/0000-0001-5992-4468)
- Chantal Scheepbouwer (ORCID: https://orcid.org/0000-0003-4243-0095)
- Madalena Monteiro (ORCID: https://orcid.org/0000-0001-8672-9756)
- Jos Jonkers (ORCID: https://orcid.org/0000-0002-9264-9792)
- Geert Kazemier (ORCID: https://orcid.org/0000-0002-9811-3497)
- Barbara Sitek
- Bart A. Westerman (ORCID: https://orcid.org/0000-0002-9898-9616)
- John W.M. Martens (ORCID: https://orcid.org/0000-0002-3428-3366)
- Jacqueline J Cloos (ORCID: https://orcid.org/0000-0001-9150-8026)
- Winan J. van Houdt (ORCID: https://orcid.org/0000-0002-2303-3468)
- Ruud H. Brakenhoff (ORCID: https://orcid.org/0000-0003-3251-5378)
- Renske D.M. Steenbergen (ORCID: https://orcid.org/0000-0002-2327-9839)
- Geert J.L.H. van Leenders (ORCID: https://orcid.org/0000-0003-2176-9102)
- Valentina Cordo’ (ORCID: https://orcid.org/0000-0003-1373-513X)
- Nicole C.T. van Grieken (ORCID: https://orcid.org/0000-0001-9992-0760)
- Connie R. Jiménez (ORCID: https://orcid.org/0000-0002-3103-4508)
- Frank Rolfs
- Jan N.M. IJzermans (ORCID: https://orcid.org/0000-0003-3558-1039)
- Jan Köster (ORCID: https://orcid.org/0000-0002-0890-7585)
- Tong Liu (ORCID: https://orcid.org/0000-0002-1389-7051)
- Fangfei Zhang (ORCID: https://orcid.org/0000-0002-4469-1486)
- Mengge Lyu
- Hanneke W. M. van Laarhoven (ORCID: https://orcid.org/0000-0003-3546-9709)
- Xiaolu Zhan
- Robby E. Kibbelaar
- Jaco C. Knol
- Richard R. de Goeij‐de Haas
- Sander R. Piersma
Institutions
- Harbin Medical University (CN)
- University of the Punjab (PK)
- Science for Life Laboratory (SE)
- Erasmus MC (NL)
- Karolinska Institutet (SE)
- The Netherlands Cancer Institute (NL)
- Westlake University (CN)
- Third Affiliated Hospital of Harbin Medical University (CN)
- Princess Máxima Center (NL)
- Erasmus MC Cancer Institute (NL)
- Erasmus MC Transplant Institute
Publication Details
- Journal
- Cancer Cell
- Published
- 2025-05-29
- DOI
- https://doi.org/10.1016/j.ccell.2025.05.003
- Citations
- 26
- Primary Topic
- Advanced Proteomics Techniques and Applications
- Type
- article
- Field-Weighted Citation Impact
- 19.66
Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Cancer Center Amsterdam