title: ELTD1, a potential new biomarker for gliomas.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA. Rheal-Towner@omrf.org
authors.forename: Rheal A
authors.initials: RA
authors.lastname: Towner
authors.forename: Randy L
authors.initials: RL
authors.lastname: Jensen
authors.forename: Howard
authors.initials: H
authors.lastname: Colman
authors.forename: Brian
authors.initials: B
authors.lastname: Vaillant
authors.forename: Nataliya
authors.initials: N
authors.lastname: Smith
authors.forename: Rebba
authors.initials: R
authors.lastname: Casteel
authors.forename: Debra
authors.initials: D
authors.lastname: Saunders
authors.forename: David L
authors.initials: DL
authors.lastname: Gillespie
authors.forename: Robert
authors.initials: R
authors.lastname: Silasi-Mansat
authors.forename: Florea
authors.initials: F
authors.lastname: Lupu
authors.forename: Cory B
authors.initials: CB
authors.lastname: Giles
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Wren
mesh_terms: D000328:Adult; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004396:Coloring Agents; D019295:Computational Biology; D030541:Databases, Genetic; D005260:Female; D005295:Ferrocyanides; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005909:Glioblastoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D046228:Microarray Analysis; D009368:Neoplasm Transplantation; D019906:Nuclear Magnetic Resonance, Biomolecular; D051381:Rats; D011916:Rats, Inbred F344; D043562:Receptors, G-Protein-Coupled / Q000032:analysis / Q000235:genetics*
chemical_list: C428324:ADGRL4 protein, human; D014408:Biomarkers, Tumor; D004396:Coloring Agents; D005295:Ferrocyanides; D043562:Receptors, G-Protein-Coupled; C000170:ferric ferrocyanide