BACKGROUND: Glioblastoma multiforme (GBM), a high-grade glioma, is characterized by being diffuse, invasive, and highly angiogenic and has a very poor prognosis. Identification of new biomarkers could help in the further diagnosis of GBM.
OBJECTIVE: To identify ELTD1 (epidermal growth factor, latrophilin, and 7 transmembrane domain-containing protein 1 on chromosome 1) as a putative glioma-associated marker via a bioinformatic method.
METHODS: We used advanced data mining and a novel bioinformatics method to predict ELTD1 as a potential novel biomarker that is associated with gliomas. Validation was done with immunohistochemistry, which was used to detect levels of ELTD1 in human high-grade gliomas and rat F98 glioma tumors. In vivo levels of ELTD1 in rat F98 gliomas were assessed using molecular magnetic resonance imaging.
RESULTS: ELTD1 was found to be significantly higher (P = .03) in high-grade gliomas (50 patients) compared with low-grade gliomas (21 patients) and compared well with traditional immunohistochemistry markers including vascular endothelial growth factor, glucose transporter 1, carbonic anhydrase IX, and hypoxia-inducible factor 1α. ELTD1 gene expression indicates an association with grade, survival across grade, and an increase in the mesenchymal subtype. Significantly high (P < .001) in vivo levels of ELTD1 were additionally found in F98 tumors compared with normal brain tissue.
CONCLUSION: Results of this study strongly suggests that associative analysis was able to accurately identify ELTD1 as a putative glioma-associated biomarker. The detection of ELTD1 was also validated in both rodent and human gliomas and may serve as an additional biomarker for gliomas in preclinical and clinical diagnosis of gliomas.
ABBREVIATIONS: AA, anaplastic astrocytoma
AO, anaplastic oligodendroglioma
CAIX, carbonic anhydrase IX
CLIO, cross-linked iron oxide
EGF, epidermal growth factor
ELTDI, endothelial growth factor, latrophilin, and 7 transmembrane-containing protein 1 on chromosome 1
GAMMA, global microarray meta-analysis
GBM, glioblastoma multiforme
Gd-DTPA, gadolinium-diethylenetriaminepentaacetic acid
iNOS, inducible nitric oxide synthase
LGA, low-grade astrocytoma
TE, echo time
TCGA, The Cancer Genome Atlas
VEGF, vascular endothelial growth factor
VEGFR2, vascular endothelial growth factor receptor 2
*Advanced Magnetic Resonance Center
§Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma
¶Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, Utah
‖The Methodist Hospital (BV), The Methodist Neurological Institute, Houston, Texas
Correspondence: Rheal A. Towner, PhD, Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104. E-mail: Rheal-Towner@omrf.org
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Received October 27, 2011
Accepted September 18, 2012