P10.17.A GLUTAMINE METABOLISM AS A PROGNOSTIC FACTOR IN GBM AND OLIGODENDROGLIOMA

Abstract

Abstract BACKGROUND Increased uptake of principal nutrients is one of the attributes of cancer cells. A recent study has shown that glutamine, but not glucose, consumption differed markedly between gliomas and adjacent healthy tissue. However, the prognostic role of glutaminolysis or glutaminolysis-related genes (GRGs) in gliomas remains unclear. Here we sought to determine if the GRG signature correlates with glioma patient survival and if it could identify patients with different outcomes. MATERIAL AND METHODS The RNA-seq and clinical data for The Cancer Genome Atlas (TCGA) was obtained from the GlioVis webpage. We compared the expression of the GRGs (GLUD1, GLUL, GLS1, GLS2, GOT1, GOT2, GPT, GPT2, SLC1A5, and SLC7A5) between 4 non-tumor, 220 IDH wild-type (IDHwt) and 389 IDH mutant (IDHmut) gliomas, of which 154 harbored 1p/19q codeletion. We further performed unsupervised hierarchical clustering for all glioma patients and compared survival between clusters. RESULTS Our results revealed that most GRGs were differentially expressed between non-tumor, IDHwt, and IDHmut gliomas. We found that gliomas grouped into 3 clusters based on the varying GRGs expression. Eighty-eight percent of glioblastomas (GBM, IDHwt) and 19% of all IDHmut tumors were characterized by low GRGs expression. These were denoted as cluster 1, and the remaining samples belonged to clusters 2 or 3, corresponding to intermediate and high GRGs expression groups, respectively. We performed survival analysis separately for IDHwt and IDHmut gliomas and found that cluster 1 patients had the worst prognosis, regardless of IDH status. We further separated IDHmut gliomas according to 1p/19q codeletion status. Oligodendroglioma (1p/19q codeleted) patients had a median survival of 33.2 months, 134.3 months, and 169.8 months in clusters 1, 2, and 3, respectively. No cluster-dependent differences in survival were seen for astrocytoma. For IDHwt (GBM) we found that patients from clusters 1 and 2 had survival of 14 months and 25 months, respectively. Due to the small number of deceased GBM patients in cluster 3, we could not estimate the median survival. The univariate analysis confirmed that cluster membership was an independent predictor of survival in oligodendroglioma (cluster 2 and 3 vs. 1, HR 0.14; 95% CI, 0.05-0.4; p=0.0005) and GBM (cluster 1 vs. 2 and 3, HR 3.05; 95% CI, 1.5-5.9; p=0.0012). CONCLUSION The GRG signature could define metabolic groups with distinct survivals in oligodendroglioma and GBM and constitute a new prognostic factor. We are planning further investigations to confirm our findings.