165 Multiplexed urinary biomarkers identify the presence of pediatric medulloblastoma.
ABSTRACT : Our laboratory has previously reported the development of urinary biomarkers capable of identifying the presence of tumors of the central nervous system (CNS). Building on this general screening panel, we now describe a tumor-specific panel of non-invasive biomarkers detectable in urine and capable of predicting the presence of the most common malignant pediatric brain tumor, medulloblastoma.
: Urine, cerebrospinal fluid, and tissue specimens were collected from pediatric patients (<21 years of age) with pathology-proven medulloblastoma (n = 16). Zymography, ELISA, and immunohistochemistry were used to characterize a panel of putative biomarkers derived from a family of related extracellular matrix (ECM) peptidases and regulatory proteins. Results were compared between age- and sex-matched controls and subjected to univariate and multivariate statistical analyses. Biomarker levels in the medulloblastoma-specific panel were compared against levels in other categories of CNS disease (non-medulloblastoma tumors, arteriovenous malformations, moyamoya) to assess the utility of the panel in discriminating the presence of medulloblastoma.
: Analysis revealed significant elevations of 4 interrelated molecules: two proteases and two inhibitors of associated proteases (all P < 0.05) - and significant reduction of a subfamily of an inhibitory enzyme (P < 0.05) in medulloblastoma patients as compared with controls. Multiplexing pairs of these molecules provided superior accuracy compared with any individual biomarker. Receiver-operating characteristics curves for the markers showed excellent discrimination. Subgroup analysis revealed that use of this panel successfully identified medulloblastoma when compared to other categories of CNS disease.
: We report, for the first time, the identification of a specific panel of 5 functionally-related biomarkers which can be detected non-invasively in the urine and successfully predict the presence of a specific subtype of pediatric brain tumor, medulloblastoma. These data support the potential utility of urinary biomarkers in the detection of pediatric brain tumors and the possibility of tumor-specific "fingerprinting" profiles.