TY - JOUR
T1 - The pan-cancer proteome atlas, a mass spectrometry-based landscape for discovering tumor biology, biomarkers, and therapeutic targets
AU - Knol, Jaco C.
AU - Lyu, Mengge
AU - Böttger, Franziska
AU - Nunes Monteiro, Madalena
AU - Pham, Thang V.
AU - Rolfs, Frank
AU - Vallés-Martí, Andrea
AU - Schelfhorst, Tim
AU - de Goeij-de Haas, Richard R.
AU - Bijnsdorp, Irene V.
AU - Wang, Shuaiyao
AU - Zhang, Fangfei
AU - A, Jun
AU - Westerman, Bart A.
AU - Sitek, Barbara
AU - Lehtiö, Janne
AU - Koster, Jan
AU - IJzermans, Jan N. M.
AU - van Laarhoven, Hanneke W. M.
AU - Bijlsma, Maarten F.
AU - Medema, Jan Paul
AU - Henneman, Alex A.
AU - Piersma, Sander R.
AU - Brakenhoff, Ruud H.
AU - Cloos, Jacqueline
AU - Cordo', Valentina
AU - de Jong, Daphne
AU - Kazemier, Geert
AU - Koppers-Lalic, Danijela
AU - Labots, Mariette
AU - le Large, Tessa Y. S.
AU - Martens, John W. M.
AU - Meijerink, Jules P. P.
AU - Mumtaz, Madiha
AU - Scheepbouwer, Chantal
AU - Kibbelaar, Robby E.
AU - Noske, David P.
AU - Steenbergen, Renske D. M.
AU - van Grieken, Nicole C. T.
AU - van Houdt, Winan
AU - Giovannetti, Elisa
AU - van Leenders, Geert J. L. H.
AU - Jonkers, Jos
AU - Liu, Tong
AU - Yan, Meisi
AU - Zhan, Xiaolu
AU - Guo, Tiannan
AU - Jimenez, Connie R.
N1 - Publisher Copyright:
© 2025 Elsevier Inc.
PY - 2025/7/14
Y1 - 2025/7/14
N2 - 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.
AB - 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.
KW - bioinformatics
KW - biomarker/ target
KW - colorectal cancer subtypes
KW - mass spectrometry
KW - multi-cancer (sub)type classification
KW - pan-cancer
KW - proteome
UR - https://www.scopus.com/pages/publications/105006938550
U2 - 10.1016/j.ccell.2025.05.003
DO - 10.1016/j.ccell.2025.05.003
M3 - Article
C2 - 40446800
SN - 1535-6108
VL - 43
SP - 1328-1346.e8
JO - Cancer cell
JF - Cancer cell
IS - 7
ER -
