522 Metabolomic Analysis of 54 Meningiomas Reveals Distinct Metabolite Profiles in WHO 1 and WHO 2/3 Tumors

Abstract

INTRODUCTION: Meningiomas are the most common primary CNS tumor. Yet when surgical and radiation fail, no further treatments exist. Metabolomics is the study of metabolic networks and has been used to discover new treatments in cancers; however, few attempts have been made to apply metabolomics to meningiomas. METHODS: Primary tumors were obtained from surgeries at the University of Iowa. Primary tumor specimens were immediately flash-frozen in liquid nitrogen, while tissue for culture was placed on ice and immediately transferred for cell culturing. Upon reaching >90% confluence, cultures were treated with 0gy, 3gy, 10gy, or 20gy gamma radiation. Six or 72 hours after radiation the cultures were washed then flash frozen in liquid nitrogen. Metabolomic profiles were obtained with a ThermoISQ gas chromatography-mass spectrometer. Data was analyzed using MetaboAnalyst 5.0. RESULTS: Forty WHO grade 1 and fourteen WHO grade 2/3 tumors were included. Eleven tumors were also successfully cultured. Partial least squares-discriminant analysis (PLS-DA) demonstrated expected clustering of primary tumors according to pathologic grade. Among the primary tumors, 12 metabolites were found to be significantly elevated in WHO grade 2/3 tumors.In parallel, primary cell cultures were developed to test the effect of radiation on the tumors, but unsupervised clustering found that inter-tumor heterogeneity was greater than the treatment effect from radiation. CONCLUSIONS: High-grade meningiomas display distinct metabolite levels compared to benign meningiomas, suggestive of altered metabolic pathway utilization. Standard cell cultures did not reveal significant metabolic changes following radiation, but it is unclear whether this was due to technique or a true finding. Further experiments are needed to elucidate the functional implications of these findings.