Proteomic analysis of chemoresistance in bladder cancer

• Applicant: Dr. Moritz Reike
• Subject Area: Reproductive Medicine, Urology
• Term: from 2021 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 470023332

Urothelial carcinoma (UC) is one of the most diagnosed cancer worldwide in women and men. Most of these patients are newly diagnosed with non-muscle-invasive bladder cancer (NMIBC), whereas up to 30% of patients are diagnosed with a muscle-invasive bladder cancer (MIBC). MIBC is linked to significant higher mortality and shows a 5-year survival rate of 60%. Treatment of non-metastatic MIBC consists of neoadjuvant chemotherapy (NAC) followed radical cystectomy (RC). The decisions in the clinical treatment of MIBC are currently made on the basis of the histopathological findings and radiological imaging. A more personalized approach based on biomarkers could help to deliver a targeted therapy to patients. For example, RNA-based subtyping was able to predict the success of NAC in several studies and identify patients who do not benefit from NAC and should immediately undergo RC. In order to make an even more precise prediction about the response to NAC or the aggressiveness of the tumor, the analysis of the tumor proteome could help to identify basic characteristics of the different subtypes. The aim of the submitted project at the Vancouver Prostate Center in Canada is therefore to carry out a tumor proteome analysis of patients with a MIBC and, as a result, to create subtypes with the aid of various digital analysis programs.In the first step, the proteomic analysis of tissue sections of patients with a chemotherapy resistant MIBC will be performed. An already established standard protocol will be used. In the precise analysis, proteins, that are associated with a failure of the NAC, should be identified. In a further step, existing transcriptome data will be merged with the data from the proteome analysis using data analysis software (OptDis software) developed at the Vancouver Prostate Center and investigated with regard to subgroup networks. An advanced data analysis will hereinafter be performed subsequently with the open-source bioinformatics software platform Cytoscape.At the same time, a further method for subtyping the MIBC will be developed in a project-cooperation with the Center for Protein Diagnostics (ProDi) in Bochum with the help of extended tissue imaging (infrared imaging and Raman spectroscopy) in combination with artificial intelligence. The aim is to develop an extended digital histopathological finding of the MIBC.After my return, it is our goal to form a long-term cooperation between the institutions. The skills gained during my stay at the Vancouver Prostate Center will be integrated into the projects at ProDi and our Department of Urology at the Marien Hospital Herne.

• DFG Programme: WBP Fellowship
• International Connection: Canada
• Host: Professor Dr. Peter C. Black