Abstract 2986: A novel biomarker for gliomas, ELTD1

Abstract

Abstract Glioblastoma multiforme (GBM) is characterized by its diffuse, invasive and highly angiogenic nature, and has a very poor prognosis. Early diagnosis of gliomas is an important goal to increase the survival rates of this devastating cancer which has limited treatment options and low survival rates. Identification of new biomarkers could help in the further diagnosis of GBM. Our goal in this study was to determine whether or not ELTD1 could be used as a marker for glioma-related processes, and use immunohistochemistry (IHC) and molecular magnetic resonance imaging (MRI) to validate its presence in human and rodent gliomas, respectively. We used advanced data mining and a novel bioinformatics method to predict ELTD1 as a novel biomarker that is associated with gliomas. A global meta-analysis (GAMMA) of all human genes was conducted to identify gene-gene co-expression patterns that were consistent and specific across heterogeneous microarray experiments. Using the Human Proteome Reference Database (HPRD) and other experimental sources on protein cellular localizations, we screened this list of predicted glioma-associated proteins for those that were extracellular or membrane-bound, because these proteins were thought to be ideal targets for molecular imaging probes and targeting therapies since they are more likely to be accessible to injected antibodies. Validation of this marker was done with IHC which was used to detect levels of ELTD1 in human high-grade gliomas and rat F98 glioma tumors ex vivo. In vivo levels of ELTD1 in rat F98 gliomas were assessed using molecular MRI (mMRI). Dextran-coated NH2 base iron oxide nanoparticles underwent conjugation with an ELTD1-specific Ab. For determination of T2* values of the iron oxide nanoprobes in gliomas, a multiple gradient echo (MGE) method was used. In this study we identified ELTD1 as a putative glioma-associated marker via a bioinformatic method, and experimentally validated its presence in both rodent and human gliomas via IHC and molecular MRI analyses in a rodent glioma model. For IHC, ELTD1 was compared to traditional IHC markers for gliomas including VEGF (vascular endothelial growth factor), GLUT-1 (glucose transporter 1), CAIX (carbonic anhydrase IX), and HIF-1α (hypoxia inducible factor-1α). ELTD1 was found to be significantly higher (P=.03) in high-grade gliomas (50 patients) compared to low-grade gliomas (21 patients), and compared well to traditional IHC markers including VEGF, GLUT-1, CAIX and HIF-1α. Significantly high (P<0.001) in vivo levels of ELTD1 were found in F98 tumors, compared to normal brain tissue. These results strongly suggest that the associative analysis method used in this study was able to accurately identify ELTD1 as a glioma-associated biomarker, and may serve as an additional biomarker for gliomas in pre-clinical and clinical diagnosis of gliomas. 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 2986. doi:1538-7445.AM2012-2986