Abstract 5881: Transcriptomic profiling of extracellular vesicle subpopulations enables liquid biopsy-based brain tumor classification

Abstract Liquid biopsies based on circulating tumor-derived cell-free DNA (ctDNA) have become an increasingly common tool for minimally invasive diagnostic testing. However, as ctDNA does not easily cross the blood-brain barrier, cell-free DNA tests for identifying and classifying brain tumors are of limited utility. Extracellular vesicles (EVs), which carry heterogeneous protein, nucleic acid, and metabolite cargos derived from various cell types including cancer cells, are an attractive alternative to ctDNA that can cross the blood-brain barrier. Because only a small fraction of circulating EVs are derived from diseased cells, current EV-based methods for cancer detection often suffer from low signal-to-noise ratios. To circumvent this issue, we have developed an extracellular vesicle subpopulation enrichment technology that specifically targets EVs derived from diseased cells. EV subpopulation transcriptomics interrogated using machine learning and gene network analyses can distinguish healthy patients, patients with benign tumors, and patients with glioma. Known tissue markers as well as novel features provide the basis for patient stratification. Coupled with a state-of-the-art multi-omics workflow, our novel EV enrichment platform allows us to capitalize upon the powerful diagnostic information contained within EV subpopulations to identify and characterize cancers from standard blood plasma samples. Citation Format: Margie Kinnersley, Claire Seibold, Tre Blohm, Riley Kemp, Sean Lodmell, Amanda Mast, Tia Seibold, Rachel Short Miller, Kelley Van Vaerenberghe, Katie Havranek. Transcriptomic profiling of extracellular vesicle subpopulations enables liquid biopsy-based brain tumor classification [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5881.