Experimental analysis of Trp and NAD metabolism in human gliomas and integration of the experimental and modeling results of the consortium with clinical data
The central aims of subproject 2 are two-fold: i) experimental analysis of Trp and NAD metabolism and ii) integration of the experimental and modeling results of the consortium with clinical data.
Two clinically relevant metabolic pathways in glioma are Trp and NAD metabolism. In subproject 2 expression analyses of the enzymes involved in Trp and NAD metabolism as well as corresponding targeted metabolic measurements will be performed in IDH mutant and wild type glioma cells and tissues WHO°II-IV. The results of these measurements will be employed to validate and refine the model of Trp and NAD metabolism developed in subproject 1. In addition, the obtained results will be used to extract metabolic markers for the activity of specific metabolic routes in IDH mutant or wild type gliomas. Ultimately, these markers will allow stratification of glioma patients to treatments and the assessment of treatment efficacy.
The second aim of subproject 2 is to integrate our experimental and modeling results with clinical data. Public data covering low grade gliomas as well as glioblastoma will be analyzed using the model of Trp and NAD metabolism developed in subproject 1 and the AHR signature developed in subproject 3. The results of these analyses will be integrated with the available clinical data regarding 1) characteristics of the tumor such as histological type, grade and location, 2) characteristics of the patients such as age, gender and ethnicity, 3) association with symptomatic seizures or other comorbidities 4) association with treatments such as preoperative corticosteroids, anti-seizure medication or radiation therapy and 5) overall survival.