Urothelial bladder cancer (UC) has a wide tumor biological spectrum with challenging prognostic stratification and relevant therapy-associated morbidity. Most molecular classifications relate only indirectly to the therapeutically relevant protein level. We improve the pre-analytics of clinical samples for proteome analyses and characterize a cohort of 434 samples with 242 tumors and 192 paired normal mucosae covering the full range of UC. We evaluate sample-wise tumor specificity and rank biomarkers by target relevance. We identify robust proteomic subtypes with prognostic information independent from histopathological groups. In silico drug prediction suggests efficacy of several compounds hitherto not in clinical use. Both in silico and in vitro data indicate predictive value of the proteomic clusters for these drugs. We underline that proteomics is relevant for personalized oncology and provide abundance and tumor specificity data for a large part of the UC proteome ( www.cancerproteins.org ).
Nature communications. 2024 May 27*** epublish ***
Franz F Dressler, Falk Diedrichs, Deema Sabtan, Sofie Hinrichs, Christoph Krisp, Timo Gemoll, Martin Hennig, Paulina Mackedanz, Mareile Schlotfeldt, Hannah Voß, Anne Offermann, Jutta Kirfel, Marie C Roesch, Julian P Struck, Mario W Kramer, Axel S Merseburger, Christian Gratzke, Dominik S Schoeb, Arkadiusz Miernik, Hartmut Schlüter, Ulrich Wetterauer, Roman Zubarev, Sven Perner, Philipp Wolf, Ákos Végvári
Institute of Pathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. ., Institute of Pathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany., Institute of Pathology, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany., Section Mass Spectrometry and Proteomics, Campus Forschung N27 00.008, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Section for Translational Surgical Oncology and Biobanking, Department of Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany., Department of Urology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany., Department of Urology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Division of Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.