INVESTIGATION OF A LIQUID BIOPSY EXTRACELLULAR VESICLE BIOMARKER FOR BRAIN TUMOURS – THE ROLE OF A COMMON INflAMMATORY PATHWAY

Abstract AIMS Extracellular vesicles are secreted by all cells and small extracellular vesicles (EVs) 50-200nm have been inves- tigated in body fluids as a potential liquid biopsy for glioblastoma. Previous studies have identified an inflam- matory signature for EVs from glioblastoma with inflammatory proteins and pathways highlighted compared to normal controls. Inflammation is a basic tissue disease reaction responsible for pathophysiology in cardio- vascular and cerebrovascular disease as well. There is increasing evidence that patients with cardiovascular disease and metabolic syndrome may also have an increased risk of developing cancer. The aim of this study was to determine a liquid biopsy signature biomarker from plasma derived extracellular vesicles from patients with brain tumours and compare it to patients with cardiovascular disease. METHODS Extracellular vesicles were derived from plasma samples from patients with brain tumours -glioblastoma, ma- lignant meningioma and cerebral metastases (n= 29) from the Dunedin Brain Tumour database. These were compared with extracellular vesicles derived from plasma from matched controls with cardiovascular disease (n=21) from the HeartOtago database. National and Local institutional ethical approval was obtained. Extracel- lular vesicles were isolated by Size Exclusion Chromotograpy and their presence confirmed as per MISEV2023 guidelines (western blot, dynamic light scattering, transmission electron microscopy, protein quantification) EVs were sent for Proteomic analysis (n=50) and microRNA nanostring analysis (n=12) RESULTS Over 4500 proteins were analysed showing a statistically significant difference in expression in 379 between brain tumour and cardiovascular samples. Some inflammatory proteins previously identified in glioblastoma were expressed equally in both groups. 810 miRNA were detected - there was little difference in expression between the two groups. CONCLUSION The development of a liquid biopsy for brain tumours is likely to involve a multi-omic signature incorporating, proteomics, miRNA and DNA analysis. Differentiation from other inflammatory disease states such as cardio- vascular disease as well as healthy controls may give useful information as to pathogenesis.