Page 33 - WNS 2022 Program Book-Final version_Neat

CSF proteomics for Glioma Espionage.
Terry C. Burns MD, PhD. Burns.terry@mayo.edu
Dept. Neurosurgery, Mayo Clinic, Rochester, Minnesota.
Co-author names, Cecile Riviere-Cazaux, BS, Samar Ikram MD, Lucas Carlstrom
MD, PhD,, Siobhan Chantigian BS, Masum Rahman MD, Arthur Warrington PhD
INTRODUCTION: The relative inaccessibility of glioma throughout a patient’s
disease course precludes individualized insights into tumor biology and
responses to therapeutic challenge. Serial cerebrospinal fluid (CSF) sampling
could provide an avenue to perform biomarker discovery for analytes that are
sensitive to tumor burden. To that end, we have established a CSF biorepository
to collect CSF intraoperatively and longitudinally from patients consenting to
serial LPs or Ommaya reservoirs placement for CSF biomarker discovery.
METHODS: Global proteomic CSF analysis was performed on the Somalogic
platform, an aptamer-based technology for sensitive and specific analysis of over
7,000 proteins. Ranked protein lists were generated for each patient by
comparing to a consensus CSF proteome from control patients without gliomas.
Enrichment analysis was performed to identify consistently differentially abundant
proteins across glioma samples. Paired patient samples were used to filter for
proteins that reproducibly decreased with resection and increased with
recurrence.
RESULTS: Forty-four proteins met specified selection criteria. This candidate
high-grade glioma proteomic signature was then evaluated in an independent
cohort of twelve glioma patients, as compared to a separate control cohort,
revealing significant signature enrichment (FDR=0.000) in all patients. When
available, comparison of post-resection to pre-resection serial samples revealed
decline in the glioma proteomic signature. Top enriched proteins included
LANC2, DPYL3, Sorcin, Integrin A1B1, and lactate dehydrogenase (FC of glioma
vs. control: 145.3x, 113.9x, 78.0x, 71.6x, and 62.7x, respectively). Interestingly,
despite having explicitly chosen samples with little-to-no hemoglobin in the
discovery cohort, this HGG signature was also highly enriched for plasma-like
proteins, illustrating the impact of blood-brain barrier disruption on the high-grade
glioma CSF proteome.
CONCLUSION: our data demonstrate the presence of a conserved CSF glioma
proteome that reflects glioma biology and the impacts of blood-brain barrier
disruption. Our findings support the feasibility of leveraging this proteome for

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