CBM-17: INCREASING EXPRESSION OF GLUTAMINASE C (GAC) mRNA IN MALIGNANT GLIOMAS

BACKGROUND: Metabolic reprogramming is the biological hallmarks of cancer cells. Glutamine metabolism, as well as aerobic glycolysis known as the Warburg effect, participate in energy formation, redox homeostasis and micromolecular synthesis to enhance tumor growth and keep malignancy, but the clinical implications are not well understood. AIMS: Through an integrated analysis of clinical glioma imaging and samples, we examined the importance of glutamine metabolism. METHODS: To identify the expression of in vivo metabolites, metabolic profiling of tumor targets from preoperative imaging was performed with MR spectroscopy (MRS) and analyzed by LC-model software in 37 glioma patients. The expression of enzymes to regulate glutamine metabolism was examined in 30 glioma samples obtained by surgical resection. RESULTS: MRS data showed that glutamine, glutamate and glutathione levels were significantly higher in glioblastomas (GBMs, WHO grade IV) than in low grade gliomas (WHO grade II) (Tukey-Kramer honest significance test, P< 0.05). Gene expression analysis demonstrated that the levels of solute-linked carrier family A1 member 5 (SLC1A5, glutamine transporter) and glutaminase C (GAC), a splice variant of glutaminase (GLS) were frequently elevated in GBMs (P< 0.05). Interestingly the expression of c-Myc was significantly correlated with GAC levels in GBMs (correlation coefficient r = 0.5855, p < 0.01). CONCLUSIONS: Glutamine metabolism plays an important role in malignant glioma. GAC could be useful diagnostic markers and therapeutic targets in the treatment of patients.