title: F11R is a novel monocyte prognostic biomarker for malignant glioma.
abstract: OBJECTIVE
  Brain tumors (gliomas) contain large populations of infiltrating macrophages and recruited microglia, which in experimental murine glioma models promote tumor formation and progression. Among the barriers to understanding the contributions of these stromal elements to high-grade glioma (glioblastoma; GBM) biology is the relative paucity of tools to characterize infiltrating macrophages and resident microglia. In this study, we leveraged multiple RNA analysis platforms to identify new monocyte markers relevant to GBM patient outcome.
  
  
  METHODS
  High-confidence lists of mouse resident microglia- and bone marrow-derived macrophage-specific transcripts were generated using converging RNA-seq and microarray technologies and validated using qRT-PCR and flow cytometry. Expression of select cell surface markers was analyzed in brain-infiltrating macrophages and resident microglia in an induced GBM mouse model, while allogeneic bone marrow transplantation was performed to trace the origins of infiltrating and resident macrophages. Glioma tissue microarrays were examined by immunohistochemistry, and the Gene Expression Omnibus (GEO) database was queried to determine the prognostic value of identified microglia biomarkers in human GBM.
  
  
  RESULTS
  We generated a unique catalog of differentially-expressed bone marrow-derived monocyte and resident microglia transcripts, and demonstrated that brain-infiltrating macrophages acquire F11R expression in GBM and following bone-marrow transplantation. Moreover, mononuclear cell F11R expression positively correlates with human high-grade glioma and additionally serves as a biomarker for GBM patient survival, regardless of GBM molecular subtype.
  
  
  CONCLUSIONS
  These studies establish F11R as a novel monocyte prognostic marker for GBM critical for defining a subpopulation of stromal cells for future potential therapeutic intervention.
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Winnie W
authors.initials: WW
authors.lastname: Pong
authors.forename: Jason
authors.initials: J
authors.lastname: Walker
authors.forename: Todd
authors.initials: T
authors.lastname: Wylie
authors.forename: Vincent
authors.initials: V
authors.lastname: Magrini
authors.forename: Jingqin
authors.initials: J
authors.lastname: Luo
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Emnett
authors.forename: Jaebok
authors.initials: J
authors.lastname: Choi
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Cooper
authors.forename: Malachi
authors.initials: M
authors.lastname: Griffith
authors.forename: Obi L
authors.initials: OL
authors.lastname: Griffith
authors.forename: Joshua B
authors.initials: JB
authors.lastname: Rubin
authors.forename: Gregory N
authors.initials: GN
authors.lastname: Fuller
authors.forename: David
authors.initials: D
authors.lastname: Piwnica-Worms
authors.forename: Xi
authors.initials: X
authors.lastname: Feng
authors.forename: Dolores
authors.initials: D
authors.lastname: Hambardzumyan
authors.forename: John F
authors.initials: JF
authors.lastname: DiPersio
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Mardis
authors.forename: David H
authors.initials: DH
authors.lastname: Gutmann
mesh_terms: D000818:Animals; D015415:Biomarkers; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D016000:Cluster Analysis; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism*; D060787:Neoplasm Grading; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; C407243:F11R protein, human; C498686:F11r protein, mouse; D011956:Receptors, Cell Surface