TAMI-77. CHARACTERIZATION OF METABOLIC DIFFERENCES IN MENINGIOMAS USING TUMOR TISSUE AND PATIENT-DERIVED CELL LINES

Abstract

Abstract As more information emerges on metabolic changes in brain pathologies, mass spectrometry methodologies are needed to investigate cellular changes in primary brain tumors. Many approaches use technologies that lack sensitivity and selectivity, which hinders discovering potential novel diagnostic and prognostic features. Fresh frozen tissue from 26 patients (57% women, 43% men, age 21-67) underwent surgical resection for newly diagnosed meningiomas. We used patient-derived cell lines and arachnoid cells to validate and compare metabolic differences in patient tumor tissue. Primary metabolism (GC-TOF), lipidomics, and biogenic amines (RPLC and HILIC-HRMS) were analyzed using 10 mg of tissue and 1x106 cells. RESULTS: Primary metabolism and lipidomics showed significant differences between Grade I and Grade II tumors. We identified over one thousand total metabolites through authentic standards and MS2 fragmentation patterns. Ascorbic Acid was enriched in Grade I tumors compared to Grade II and enriched in tumors compared to non-neoplastic dura tissue from the same patient. Lysosomal activation in atypical meningiomas is indicated by a 2-fold increase (compared to Grade I tumors) of Bis(monoacylglycero)phosphate metabolites. We grouped metabolites into fifteen classes based on chemical ontology and function. Statistically significant differences were observed in total amino acids (AA), basic AA, cyclic AA, sulfur-containing AA, branched-chain AA, dipeptides, histidine-containing dipeptides, vitamins and cofactors, glutathione metabolites, acylcarnitine’s, sphingomyelins, phosphatidylethanolamines, phosphatidylinositol’s, cardiolipins, and nucleic acids. Thymine-containing nucleic acids and biogenic monoamines were 2-fold higher in Grade I compared to Grade II tumors. Using novel untargeted metabolomics, we found multiple classes of metabolites that were enriched in Grade II meningiomas compared to Grade I. This points towards possible pathways that drive malignancy and biomarkers that could be useful for diagnosis, grading, and treatment selection.