Journal Article

Proteomic analysis of the urothelial cancer landscape

Roesch, Marie C., Diedrichs, Falk, Struck, Julian P., Offermann, Anne, Hennig, Martin, Mackedanz, Paulina, Schoeb, Dominik S., Dressler, Franz F., Gemoll, Timo, Kramer, Mario W., Sabtan, Deema, Schlüter, Hartmut, Végvári, Ákos, Zubarev, Roman, Perner, Sven, Krisp, Christoph, Wetterauer, Ulrich, Voß, Hannah, Merseburger, Axel S., Wolf, Philipp, Hinrichs, Sofie, Kirfel, Jutta, Gratzke, Christian, Miernik, Arkadiusz, Schlotfeldt, Mareile

2024

Overview

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 ). Urothelial cancer is a challenging disease and an emerging field for targeted therapies. Here, the authors optimize clinical proteomics to provide proteome-level data on tumor specificity and identify robust prognostic subtypes with predictive information for repurposed drug candidates.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/45/475 / 692/308/575 / 692/4017 / 692/4028/67/589/1336 / 692/53/2423 / 82/29 / 82/51 / 82/58 / Aged / Aged, 80 and over / Biomarkers / Biomarkers, Tumor - metabolism / Bladder cancer / Cancer / Drug development / Female / Humanities and Social Sciences / Humans / Male / Middle Aged / Morbidity / multidisciplinary / Prognosis / Proteome - metabolism / Proteomes / Proteomics / Proteomics - methods / Robustness / Science / Science (multidisciplinary) / Tumors / Urinary Bladder Neoplasms - genetics / Urinary Bladder Neoplasms - metabolism / Urinary Bladder Neoplasms - pathology / Urothelial cancer / Urothelium - metabolism / Urothelium - pathology