Abstract 4633: Urinary biomarkers predict the presence of ependymoma non-invasively
Authors: Sesen Julie , Luiselli Gabrielle , Moses-Gardner Alexander , Pineda Stephen , Duggins-Warf Micah , Gruber Maxwell , Proctor Maxwell , Smith Edward R. 
Published: August 2018

Abstract
Objective: Pediatric brain tumors persist as a diagnostic and therapeutic challenge. The ability to identify a specific tumor diagnosis and non-invasively monitor the patient's response to therapy would serve as a major clinical advancement which could directly impact current practice. Knowing the tumor identity pre-operatively can influence surgical planning, so novel methods to improve upon existing imaging tools would help neurosurgeons treat children more effectively. In addition, post-operative follow-up of brain tumors currently relies on frequent imaging studies, which often requires the cost and risk of general anesthesia in children to facilitate scanning. Ependymoma is one of the most common pediatric brain tumors that can often mimics other pathologies on imaging reports, and typically requires extensive follow-up. Here, we present a novel method of utilizing non-invasive urinary biomarkers to diagnose pediatric ependymomas.
Methods: Urine was collected from 107 children with brain tumors, including a cohort with pathology-proven ependymoma (n = 19) and age- and sex-matched controls (n = 17). Using a previously validated screening panel of secreted proteins associated with tumor growth, including matrix metalloproteinases (MMPs), growth factors, and cytokines, putative biomarker levels were quantified using multiplex and ELISA assays in urine. Results were subjected to univariate and multivariate statistical analyses and compared between clinical cohorts. Once identified, further validation of biomarker expression was performed using in vitro analysis of primary tumor and control cell lines to link biomarker expression to source tissue.
Results: Evaluation of urinary biomarkers by multiplex and ELISA revealed that patients with ependymoma demonstrated significantly higher levels of urinary MMP3 and MMP9 as compared to healthy children. We identified clinically relevant cut-off values to identify the presence of tumor; &gt;0.25 pg/µg for MMP-3 and &gt;1.00 pg/µg for MMP-9. Multiplexing biomarkers markedly increased diagnostic accuracy. Urinary biomarker expression was correlated with in vitro cell lines, indicating that ependymoma tumor tissue is the source of the biomarkers.
Conclusions: We report for the first time the use of urinary proteins—MMP3 and MMP9— as biomarkers capable of identifying the presence of ependymoma non-invasively and with high accuracy. This study provides substantial in vitro and clinical data supporting the utility of urinary biomarkers as a novel tool to advance the diagnosis and treatment of pediatric brain tumors.
Citation Format: Julie Sesen, Gabrielle Luiselli, Alexander Moses-Gardner, Stephen Pineda, Micah Duggins-Warf, Maxwell Gruber, Maxwell Proctor, Edward R. Smith. Urinary biomarkers predict the presence of ependymoma non-invasively [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4633.