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. 2025 Jul 14;43(7):1328-1346.e8.
doi: 10.1016/j.ccell.2025.05.003. Epub 2025 May 29.

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

Jaco C Knol  1 , Mengge Lyu  2 , Franziska Böttger  1 , Madalena Nunes Monteiro  1 , Thang V Pham  1 , Frank Rolfs  1 , Andrea Vallés-Martí  1 , Tim Schelfhorst  1 , Richard R de Goeij-de Haas  1 , Irene V Bijnsdorp  3 , Shuaiyao Wang  2 , Fangfei Zhang  4 , Jun A  2 , Bart A Westerman  5 , Barbara Sitek  6 , Janne Lehtiö  7 , Jan Koster  8 , Jan N M IJzermans  9 , Hanneke W M van Laarhoven  10 , Maarten F Bijlsma  11 , Jan Paul Medema  11 , Alex A Henneman  1 , Sander R Piersma  1 , Ruud H Brakenhoff  12 , Jacqueline Cloos  13 , Valentina Cordo'  14 , Daphne de Jong  15 , Geert Kazemier  16 , Danijela Koppers-Lalic  17 , Mariette Labots  18 , Tessa Y S Le Large  16 , John W M Martens  19 , Jules P P Meijerink  14 , Madiha Mumtaz  20 , Chantal Scheepbouwer  21 , Robby E Kibbelaar  22 , David P Noske  17 , Renske D M Steenbergen  23 , Nicole C T van Grieken  24 , Winan van Houdt  25 , Elisa Giovannetti  18 , Geert J L H van Leenders  26 , Jos Jonkers  27 , Tong Liu  28 , Meisi Yan  29 , Xiaolu Zhan  30 , Tiannan Guo  31 , Connie R Jimenez  32
Affiliations

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

Jaco C Knol et al. Cancer Cell. .

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.

Keywords: bioinformatics; biomarker/ target; colorectal cancer subtypes; mass spectrometry; multi-cancer (sub)type classification; pan-cancer; proteome.

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Conflict of interest statement

Declaration of interests T.G. is a shareholder of Westlake Omics Inc.; M.F.B. has received research funding from Celgene, Frame Therapeutics, and Lead Pharma and has acted as consultant to Servier, Olympus, and Wholomics; R.D.M.S. is a minority shareholder of Self-screen BV and received consultancy fee from AstraZeneca.

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