Project Details
Projekt
Spatial transcriptome mapping for comprehensive elucidation of tumor heterogeneity for prognosis and therapy resistance in renal cell carcinoma
Applicants
Professor Dr. Matthias Schwab; Dr. Elke Schäffeler
Subject Area
Reproductive Medicine, Urology
Pharmacology
Pharmacology
Term
since 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 497304248
Although targeted therapies including immunotherapeutic strategies are already used for treatment of renal cell carcinoma (RCC), the 5-year survival rate for patients with metastatic disease is still <20%. Moreover, up to 40% of patients with primarily localized RCC experience disease relapse and therapy resistance is a major issue in RCC treatment. Reliable prognostic biomarkers for patient stratification based on recurrence risk or therapeutic response are missing in localized and metastatic RCC. Genetic intratumor heterogeneity (ITH) represents a major issue in RCC and might complicate valid risk prediction and therapy response. In the present project, we aim to investigate comprehensively transcriptional ITH using an unique prospectively collected study population of 60 RCC patients comprising fresh frozen tumor material from at least 3 regions per primary tumor. Tumor material has been already characterized on the genetic (whole genome genotyping via microarry analysis, panel sequencing) and global transcriptomic level. Spatial gene expression profiling will be performed in intact tissue cryosections in the morphological context using the innovative Visium Spatial Transcriptomics Technology (10xGenomics) which includes staining of tissues and subsequent NGS analyses. Gene signatures of distinct heterogenous tissue regions, including tumor, stroma and immune infiltrates will be identified through combination of histology and spatially resolved whole transcriptome analysis for better understanding of tumor progression and therapy resistance. In addition comprehensive analysis of mutational burden in tumor areas will be considered.
DFG Programme
Research Grants
