Abstract 1266: Glioma biomarker discovery by mass spectrometry

Abstract

Abstract BACKGROUND Approximately 200.000 people are diagnosed with a primary brain tumor each year worldwide. The most common type of primary brain tumor (∼40%) are gliomas. Currently available prognostic markers require evaluation of tumor tissue, such as 1p and 19q choromosome co-deletion in oligodendroglial tumors, MGMT promoter methylation for glioblastomas (GBMs), and IDH mutations in several glioma subtypes. Serum biomarkers that correlate with tumor status have prognostic and predictive value and could significantly improve the care for glioma patients. In addition biomarkers could provide unique information related to longitudinal response to therapy. The only clinically validated serum marker of prognosis and disease status in high grade gliomas is serum YKL-40, a chitinase homolog also called human cartilage glycoprotein 39 or chitinase 3-like 1. DESIGN/METHODS For the discovery phase we used a set of 31 cerebrospinal fluid samples. This sample set included 5 CSF samples of patients with a GBM and 26 controls. These samples were digested by trypsin and subsequently measured by LCMS-Orbitrap. The acquired data were analyzed using a database search and a subsequent analyses of the spectral counts by Scaffold. The spectral counts for each individual identified protein are used as a semi quantitative measure for protein abundance. RESULTS / CONCLUSIONS From the total list of 771 identified proteins, candidate biomarker proteins were selected that showed a significant difference between the control and GBM (p<0.01) and were at least 3 fold higher in spectral count than in the control group. Abundant serum proteins were removed to avoid inclusion of proteins that relate to the disruption of the blood-CSF barrier. Eventually, a list of eleven proteins was obtained that included 14-3-3 protein gamma, 72 kDa type IV collagenase, Alpha-enolase, Chitinase-3-like protein 1 (YKL-40), Fetuin-B, Glial fibrillary acidic protein, Insulin-like growth factor II, Metalloproteinase inhibitor 1, Serum paraoxonase/arylesterase 1, SPARC, IGF binding protein 2 and Metalloproteinase inhibitor 2. Many of the identified candidate markers have been previously reported in literature in relation to glioma including the clinically validated serum marker for glioma YKL-40. We are now planning a validation of these markers in a set of serum samples of glioma patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1266. doi:1538-7445.AM2012-1266