Plasma Lipidomics as a Novel Liquid Biopsy Approach for Glioblastoma

Glioblastoma is an aggressive brain tumor that invariably recurs despite treatment, partly due to metabolic adaptations, including altered lipid metabolism. This study investigates plasma lipidomic profiles in glioblastoma patients to explore their potential as a liquid biopsy for disease monitoring. Plasma samples were collected from 36 patients with histopathologically-confirmed IDH wild-type glioblastoma at four treatment stages: Pre-Surgery (n=36), Post-Surgery (n=32), Pre-Radiation (n=28), and Post-Radiation (n=17). Untargeted lipidomics analysis was performed using liquid chromatography-high resolution mass spectrometry (LC-HR-MS/MS. Plasma lipidomic signatures differed significantly across treatment stages. Specifically, the lipidomic profile prior to surgery was distinct from those at subsequent stages, demonstrating increased compound abundance of numerous lipids prior to surgery that are decreased at subsequent stages, including linolenic acid (fold change 2.58, p=4.21x10-11), behenic acid (fold change 2.09, p=9.3x10-10), and linolenic acid (fold change 4.44, p=5.83x10-6). Random Forest modeling could predict pre-surgical samples with 85.7% accuracy. Plasma lipidomics shows promise as a liquid biopsy approach for monitoring glioblastoma treatment. The distinct lipidomic profile observed prior to surgery suggests potential for early detection.