1244. Title: Protein Biomarker Discovery in Patients with Intracranial Aneurysms

Authors: Dominic A. Nistal; Nicolas Fernandez, PhD; Seunghee Kim-Schulze, PhD; Jonah Stein, BA; Ryan Adams, BA; J Mocco, MD, MS; Christopher Kellner, MD (New York, NY)

Introduction: Intracranial aneurysms occur in approximately 1-2% of the general population and are the leading cause for subarachnoid hemorrhage (SAH). Recent studies have shown that inflammatory and cell adhesion molecules, as well as cerebral proteins related to brain and vascular damage, are associated with the formation and progression of aneurysmal growth. In this study, we utilized proteomic data from patients with known intracranial aneurysms to identify a protein expression signature to detect the presence of a cerebral aneurysm. Methods: Twenty-eight patients with unruptured intracranial aneurysms were prospectively enrolled in this study. Protein, RNA, and whole blood DNA were isolated from peripheral blood samples and sent for processing. Protein expression levels were determined using the Proseek multiplex immunoassay, inflammatory panel (http:// www.olink.com /). Analyte datawas visualized and analyzed using the Clustergrammer Jupyter widget. The patient a nalyte data was hierarchically clustered, enrichment of patient clusters for clinical parameters was assessed using the binomial proportions test, and patient-cluster signatures were generated using the student's T-test. Results: Of the twenty-eight patients, 82.1% (n=23) were female, 46.4% (n=13 ) were never smokers, 35.7% (n=10) were former smokers, and 17.9% (n=5) were current smokers. The mean aneurysm size was 8.9mm with the most common location being anterior communicating artery (35.7%, n=10). After normalization, 72 analytes were measured across the subject population. When subjects were separated into the three smoking categories, significant differences in protein expression were identified for 13 analytes. VEGFA showed the greatest expression difference when never smokers were compared to the remaining cohort (p=0.0085). Conclusion: In this study, we utilize clinical data from patients with intracranial aneurysms and identify differential expression signatures that align with the clinical parameters, such as smoking history. Comparison to a control population will allow for the development of a more sophisticated signature taking into account a number of different parameters.