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

Knol JC, Lyu M, Böttger F, Nunes Monteiro M, Pham TV, Rolfs F, Vallés-Martí A, Schelfhorst T, de Goeij-de Haas RR, Bijnsdorp IV, Wang S, Zhang F, A J, Westerman BA, Sitek B, Lehtiö J, Koster J, IJzermans JNM, van Laarhoven HWM, Bijlsma MF, Medema JP, Henneman AA, Piersma SR, Brakenhoff RH, Cloos J, Cordo' V, de Jong D, Kazemier G, Koppers-Lalic D, Labots M, Le Large TYS, Martens JWM, Meijerink JPP, Mumtaz M, Scheepbouwer C, Kibbelaar RE, Noske DP, Steenbergen RDM, van Grieken NCT, van Houdt W, Giovannetti E, van Leenders GJLH, Jonkers J, Liu T, Yan M, Zhan X, Guo T, Jimenez CR

Cancer Cell 43 (7) 1328-1346.e8 [2025-07-14; online 2025-05-29]

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.

PubMed 40446800

DOI 10.1016/j.ccell.2025.05.003

Crossref 10.1016/j.ccell.2025.05.003

pii: S1535-6108(25)00212-0