SITH · Proteomic segmentation of intratumour heterogeneity for identifying clinically relevant tumour subpopulations in gastrointestinal cancers

An important factor that influences therapy response and prognosis of cancer patients has been identified as intratumoral heterogeneity. Gastrointestinal cancers are known to be morphologically and molecularly very heterogeneous diseases. Thus, there is a strong need to identify clinically relevant tumor subpopulations and characterize their genetic and proteomic features. A novel technology which allows the untargeted and spatially resolved analysis of the molecular content of tissues while preserving the histology of the tissue sections is MALDI (matrix-assisted laser desorption/ionization) imaging mass spectrometry, in short MALDI imaging. It has been demonstrated that MALDI imaging constitutes a unique tool to discover tumor subpopulations based solely on the detected mass spectrometry profiles that are not distinguishable by conventional histopathological methods. The objectives of this project are (i) to identify clinical relevant tumor subpopulations by MALDI imaging in gastrointestinal cancers with regard to disease outcome and metastasis as clinical endpoints, and (ii) to characterize the molecular properties of these subpopulations on a genetic, proteomic, and metabolomic level. This could provide more knowledge about the biology of tumors and their molecular variance, and result in novel markers for therapy prediction or prognosis of patients, thus aiding the progress towards more personalized-medicine.""