TPCPA offers a wealth of data that are freely accessible via http://r2platform.com/TPCPA. This atlas allows researchers world-wide to discover new biomarkers and therapeutic targets. It is an important step towards achieving better diagnoses and more effective therapies.
Why a focus on proteins?
Jimenez explains that proteins underlie all functions in our body and that their activity is disregulated in cancer. Many proteins are used as drug targets for targeted therapy in the clinic. Thusfar, large-scale cancer research has been largely based on DNA research, but aberrations at that level are not always relevant. And that’s why proteins were analyzed. “With the advent of a revolutionary new measurement technique, we have now been capable of mapping protein profiles in almost 1000 tumors”. The Atlas has been established with advanced mass spectrometry, using a special “parallel” measurement design that determines composition, quantity, and molecular state of (most) proteins within a tissue in a single measurement. “The dataset of almost 10.000 proteins offers new insights in cancer biology on an individual basis as well as opportunities for the development of more accurate diagnostics and personalized treatments”, Jimenez continues.
New biomarkers and therapeutic targets
TPCPA provides insight in processes and functions of proteins that play a role in 22 forms of cancer. One of the first authors, Jaco Knol: “For every tumor type, we identified the top 10 proteins that are most compelling for tests in follow-up research. Enzymes like HERC5 (esophageal cancer) and RNF5 (liver cancer) offer opportunities for innovative therapies that induce the degradation of tumor proteins.” Furthermore, biomarkers were found for the discrimination of four subtypes of colorectal cancer with different biology. “In turn such tumors can also be divided in two subtypes with different immune cell infiltration. These classifications can help predict prognosis in colon cancer. Another important achievement is that we developed a protein signature for the prediction of the primary tissue origin of tumor metastases. This is crucial for the adequate treatment of patients with metastasized cancer since the origin of ~5% of metastases is unknown”, says Knol.
The TPCPA findings show the value of high-throughput proteome profiling for tumor characterization, and provides insights in the heterogeneity of cancer as a disease with possible clinical implications. Via the data portal, it offers a queryable treasure trove of data for hypotheses for more specifically targeted research.
Graphical summary of TPCPA
Link to the full article: The pan-cancer proteome atlas, a mass spectrometry-based landscape for discovering tumor biology, biomarkers, and therapeutic targets
Involved researchers:
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 Lehtio, Jan Koster, Jan N.M. IJzermans, Hanneke W. M. van Laarhoven, Maarten F. Bijlsma, Jan Paul Medema, Alex A. Henneman, Sander R. Piersma, Ruud H. Brakenhoff, Jacqueline Cloos, Valentina Cordo, Daphne de Jong, Geert Kazemier, Danijela Koppers-Lalic, Mariette Labots, Tessa Y.S. Le Large, John W. M. Martens, Jules P. P. Meijerink, Madiha Mumtaz, Chantal Scheepbouwer, Robby E. Kibbelaar, David Noske, Renske D. M. Steenbergen, Nicole C. T. van Grieken, Winan van Houdt, Elisa Giovannetti, Geert J. L.H. van Leenders, Jos Jonkers, Tong Liu, Meisi Yan, Xiaolu Zhan, Tiannan Guo, and Connie R. Jimenez.
Researchers in bold are affiliated with Cancer Center Amsterdam.
Funders involved:
Cancer Center Amsterdam and the Netherlands Organization for Scientific Research (NWO Middelgroot, #91116017) are acknowledged for support of proteomics infrastructure. This work was further supported by project grants of the Dutch Cancer Society to C.R.J (KWF VU-6816, KWF-VU10212 and KWF-VU12516), KWF- UvA2013-6331 to J.P.M. and C.R.J., KWF-EMCR 2015-8022 to C.R.J. (coPI), KWF2016_10355 to J.P.M. and C.R.J., Netherlands eScience (ASDI.2020.014) to C.R.J. and T.V.P., and National Key R&D Program of China (Grant No. 2021YFA1301600) to T.G.
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