BIOM-52. THE DYNAMIC GLIOMA CSF PROTEOME: IMPACT OF LOCATION AND RESECTION FOR DISEASE MONITORING

Abstract While serial sampling of glioma tissue is rarely performed before recurrence, cerebrospinal fluid (CSF) can be acquired serially to evaluate candidate monitoring and pharmacodynamic biomarkers in patients with gliomas. However, the impact of key variables to consider in longitudinal CSF, including anatomical location and post-surgical changes, remains unknown. To that end, pre- versus post-resection intracranial CSF samples from patients with gliomas were obtained at early (1-16 days; n=20) or delayed (86-153 days; n=11) timepoints, as well as lumbar-versus-intracranial glioma CSF samples (n=14). Using aptamer-based proteomics, we identified significant differences in the glioma CSF proteome between lumbar, subarachnoid, and ventricular CSF. Indeed, intracranial CSF in paired lumbar/intracranial samples had nearly 1600 unique aptamers, regardless of which intracranial location was compared to the paired lumbar CSF, including in enrichment style analyses that evaluated the overlap between protein states. Importantly, resection had a significant, evolving longitudinal impact on the CSF proteome, with subsets of proteins associated with early versus delayed post-resection changes, many of which were enriched for inflammatory-related pathways. Interestingly, despite increased contamination from surgical debris, enrichment for plasma-associated proteins decreased with resection (FDR: 0.000), suggesting that a portion of the baseline glioma panel could be derived from plasma-originating analytes due to blood-brain barrier disruption. Despite these challenges, our data still revealed preliminary candidate monitoring biomarkers, such as brevican, that increased with progression (example patient: fold-change of 3.58x and 2.08x through lomustine and bevacizumab, respectively), but not pseudoprogression (Fold change less than 1.5). Serial intracranial CSF samples suggested the early potential for disease monitoring and evaluation of pharmacodynamic impact of targeted therapies, including bevacizumab and pembrolizumab. In conclusion, our available data to date suggest that the intracranial glioma CSF proteome provides an abundant and evolving source of candidate biomarkers to longitudinally discern the impact of resection and systemic treatments.