CSIG-01. DECREASING EXPRESSION OF TRAF PROTEINS WITH INCREASING MALIGNANCY WITH LOWEST EXPRESSION IN IDH-WILDTYP GLIOBLASTOMA

Abstract The tumor necrosis factor receptor-associated factors (TRAF) are cytoplasmatic adapter proteins that can interact directly with the intracellular domains of cell surface receptors, such as the TNF receptor superfamily. TRAFs are thus involved in cellular processes like proliferation or apoptosis. Seven members are known; all expressed in the cytosol of various cell and tissue types. Increased levels of TRAF4 in GBM tissue are related to cell proliferation and migration. About 25 % of grade I meningioma show mutations in TRAF7, which are associated with a lower risk of malignant transformation. Therefore expression patterns of all seven TRAF members are evaluated in different glioma grades. Following tumor samples were obtained during neurosurgery and shock frozen in liquid nitrogen: peritumoral tissue, astrocytoma and oligodendroglioma (G2, G3) and glioblastoma (primary and recurrent). Transcription rate of TRAF1-7 was measured via qPCR. Correlation of TRAF expression level and patient overall survival was evaluated using TCGA datasets of the TCGA-LGG” and “TCGA-GBM” projects. With the exception of TRAF5, a decreased mRNA level with increasing malignancy could be found for all TRAFs (TRAF1 p=n.s.; TRAF2 p=0.0026; TRAF3 p<0.0001; TRAF4 p=0.0021; TRAF6 p<0.0001; TRAF7 p<0.0001). IDHwt glioblastoma showed significant lower expression level compared to IDHmut glioblstoma in all TRAFs except for TRAF1 (TRAF2 p<0.0001; TRAF3 p=0.0346; TRAF4 p<0.0001; TRAF6 p=0.0447; TRAF7 p=0.0081). TRAF5 again showed a reverse effect (p=0.0065). Correlation of TRAF expression level in low grade glioma and patient survival revealed longer overall survival with low TRAF1,2,4 and TRAF5 expression (p<0.0001, p= 0.0178, p=0.0307, p<0.0001). No difference in survival rate in high grade glioma could be found.