Integration of molecular pathological and digital pathological information for a more precise prediction of prognosis in colorectal cancer

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Colorectal cancer is a heterogeneous disease that can be classified according to the different underlying molecular pathogenesis. Colorectal carcinomas that have developed over the same molecular pathway are also likely to be similar in their response to therapy and their prognosis. The investigation of subtypes of colorectal cancer, which can be distinguished from each other by molecular pathological and clinical characteristics, holds an enormous translational potential. With the help of the DFG follow-up proposal, the tumor analyses of patients in the DACHS study will be expanded to specifically address questions of precision medicine on the therapeutic response and prognosis in colorectal cancer. For this purpose, the main tumor subtypes MSI, CIMP, BRAF and KRAS will be determined in another 1300 patients of the DACHS study in order to increase the total number to 3500 for the planned analyses. Also, to integrate other promising and clinically relevant biomarkers into the analyses, additional tumor markers will be investigated. Until recently, genome-wide methylation information from tumor tissue has been available for about 1000 patients of the DACHS study, which has been analyzed and published with regard to its prognostic significance. In the meantime, the number of patients with genome-wide methylation information has increased to >2100. Within this project, this much larger patient population will be used to carry out more specific and more meaningful analyses. Another promising new tumor marker is the Immunoscore, a prognostic score that has been established in large validation studies. The Immunoscore is a promising prognostic score that has been established in large validation studies. However, its role in staging and treatment, as well as in combination with other molecular markers, has not yet been well studied, as such studies require large patient populations. It is planned to determine the Immunoscore for 2000 patients, which can be determined by immunohistochemical staining of the gene expression of CD3 and CD8 on paraffin sections with subsequent digital pathological evaluation, which has already been successfully tested in preliminary work.Due to the extensive preliminary work in the DACHS study, the already established analytical methods for the molecular characterization of tumor tissue, as well as the scientific expertise and interconnectedness of the applicants, the prerequisites for the investigations of prognostic and therapy-relevant associations with molecular subtypes of colorectal cancer are excellent in this follow-up project. Due to the large number of patients and the extensive patient and tumor characterization, the planned analyses have a high translational potential and will provide novel results for in the field of precision medicine.