title: Proportional upregulation of CD97 isoforms in glioblastoma and glioblastoma-derived brain tumor initiating cells.
abstract: CD97 is a novel glioma antigen that confers an invasive phenotype and poor survival in patients with glioblastoma (GBM), the most aggressive primary malignant brain tumor. The short isoform of CD97, known as EGF(1,2,5), has been shown to promote invasion and metastasis, but its role in gliomas and GBM-derived brain tumor initiating cells (BTICs) has not been studied. We sought to characterize CD97 expression among gliomas and identify the specific isoforms expressed. The short isoform of CD97 was identified in GBM and GBM-derived BTICs, but not low grade or anaplastic astrocytomas. All samples expressing the EGF(1,2,5) isoform were also found to express the EGF(1,2,3,5) isoform. These isoforms are believed to possess similar ligand binding patterns and interact with chondroitin sulfate, a component of the extracellular matrix, and the integrin α5β1. Using data acquired from the Cancer Genome Atlas (TCGA), we show that CD97 is upregulated among the classical and mesenchymal subtypes of GBM and significantly decreased among IDH1 mutant GBMs. Given its proven roles in tumor invasion, expression among aggressive genetic subtypes of GBM, and association with overall survival, CD97 is an attractive therapeutic target for patients with GBM.
authors.affiliation: Department of Neurological Surgery, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Safaee
authors.affiliation: Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
authors.forename: Shayan
authors.initials: S
authors.lastname: Fakurnejad
authors.affiliation: Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
authors.forename: Orin
authors.initials: O
authors.lastname: Bloch
authors.affiliation: Department of Neurological Surgery, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Clark
authors.affiliation: Department of Neurological Surgery, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Ivan
authors.affiliation: Department of Neurological Surgery, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Matthew Z
authors.initials: MZ
authors.lastname: Sun
authors.affiliation: Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
authors.forename: Taemin
authors.initials: T
authors.lastname: Oh
authors.affiliation: Department of Neurological Surgery, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Joanna J
authors.initials: JJ
authors.lastname: Phillips
authors.affiliation: Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Parsa
mesh_terms: D017398:Alternative Splicing; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D060787:Neoplasm Grading; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D059368:RNA Isoforms; D043562:Receptors, G-Protein-Coupled
chemical_list: C095004:ADGRE5 protein, human; D015703:Antigens, CD; D059368:RNA Isoforms; D043562:Receptors, G-Protein-Coupled; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human