title: Epidermal growth factor-like module containing mucin-like hormone receptor 2 expression in gliomas.
abstract: Epidermal growth factor (EGF) module-containing mucin-like receptor 2 (EMR2) is a member of the seven span transmembrane adhesion G-protein coupled receptor subclass. This protein is expressed in a subset of glioblastoma (GBM) cells and associated with an invasive phenotype. The expression pattern and functional significance of EMR2 in low grade or anaplastic astrocytomas is unknown and our goal was to expand and further define EMR2's role in gliomas with an aggressive invasive phenotype. Using the TCGA survival data we describe EMR2 expression patterns across histologic grades of gliomas and demonstrate an association between increased EMR2 expression and poor survival (p < 0.05). This data supports prior functional data depicting that EMR2-positive neoplasms possess a greater capacity for infiltrative and metastatic spread. Genomic analysis suggests that EMR2 overexpression is associated with the mesenchymal GBM subtype (p < 0.0001). We also demonstrate that immunohistorchemistry is a feasible method for screening GBM patients for EMR2 expression. Protein and mRNA analysis demonstrated variable expression of all isoforms of EMR2 in all glioma grades, however GBM displayed the most diverse isoforms expression pattern as well as the highest expression of the EGF1-5 isoform of EMR2. Finally, a correlation of an increased EMR2 expression after bevacizumab treatment in glioma cells lines is identified. This observation should serve as the impetus for future studies to determine if this up-regulation of EMR2 plays a role in the observation of the diffuse and increasingly invasive recurrence patterns witnessed in a subset of GBM patients after bevacizumab treatment.
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, CA, USA, ivanm@neurosurg.ucsf.edu.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Ivan
authors.forename: Michael
authors.initials: M
authors.lastname: Safaee
authors.forename: Taemin
authors.initials: T
authors.lastname: Oh
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Clark
authors.forename: Matthew Z
authors.initials: MZ
authors.lastname: Sun
authors.forename: Joseph
authors.initials: J
authors.lastname: Kim
authors.forename: Orin
authors.initials: O
authors.lastname: Bloch
authors.forename: Arman
authors.initials: A
authors.lastname: Jahangiri
authors.forename: Joanna J
authors.initials: JJ
authors.lastname: Phillips
authors.forename: Manish K
authors.initials: MK
authors.lastname: Aghi
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Parsa
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D000068258:Bevacizumab; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008819:Mice, Nude; D060787:Neoplasm Grading; D009368:Neoplasm Transplantation; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
chemical_list: C412456:ADGRE2 protein, human; D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D020033:Protein Isoforms; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D000068258:Bevacizumab