title: Diagnostic and prognostic value of preoperative combined GFAP, IGFBP-2, and YKL-40 plasma levels in patients with glioblastoma.
abstract: BACKGROUND
  Circulating proteins released by tumor cells have recently been investigated as potential single surrogate biomarkers for glioblastoma multiforme (GBM). The aim of the current hypothesis-generating study was to evaluate the diagnostic and prognostic role of preoperative insulin-like growth factor-binding protein 2 (IGFBP-2), chitinase-3-like protein 1 (YKL-40), and glial fibrillary acidic protein (GFAP) plasma levels in patients with GBM, both as single markers and as a combined profile.
  
  
  METHODS
  Plasma samples from 111 patients with GBM and a subset of 40 patients with nonglial brain tumors were obtained preoperatively. Plasma from 99 healthy controls was also analyzed. IGFBP-2, YKL-40, and GFAP levels were determined using enzyme-linked immunoadsorbent assay tests. Their association with histological and radiological variables was assessed.
  
  
  RESULTS
  Circulating levels of all 3 proteins were found to be significantly higher in patients with GBM compared with healthy controls (P < .01). Only YKL-40 and GFAP were found to demonstrate significant differences between patients with GBM and nonglial brain tumors (P = .04). GFAP was undetectable (<0.02 ng/mL) in all patients without GBM. A receiver operating characteristic analysis accounting for a 2-step diagnostic procedure including the 3 biomarkers afforded an area under the curve of 0.77 for differentiating patients with GBM from those with nonglial brain tumors. There was a significant correlation between tumor volume and plasma IGFBP-2 level (Spearman Rho correlation coefficient, 0.22; P = .025) and GFAP (Spearman Rho correlation coefficient, 0.36; P < .001) among patients with GBM. Preoperative plasma IGFBP-2 levels were found to be independently associated with worse overall survival among patients with GBM (hazard ratio, 1.3; P = .05).
  
  
  CONCLUSIONS
  A combined profile of preoperative IGFBP-2, GFAP, and YKL-40 plasma levels could serve as an additional diagnostic tool for patients with inoperable brain lesions suggestive of GBM. In addition, IGFBP-2 levels appear to constitute an independent prognostic factor in patients with GBM.
authors.affiliation: Neurology Service 2, Mazarin Division, Pitié-Salpêtrière Hospital, AP-HP; Sorbonne Universités, UPMC Univ Paris 06, UM 75; CNRS, UMR 7225; Inserm, U1127; ICM, F-75013, Paris, France; Department of Neurology, Clinic of the University of Navarra, University of Navarra School of Medicine, Pamplona, Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: Gállego Pérez-Larraya
authors.forename: Sophie
authors.initials: S
authors.lastname: Paris
authors.forename: Ahmed
authors.initials: A
authors.lastname: Idbaih
authors.forename: Caroline
authors.initials: C
authors.lastname: Dehais
authors.forename: Florence
authors.initials: F
authors.lastname: Laigle-Donadey
authors.forename: Soledad
authors.initials: S
authors.lastname: Navarro
authors.forename: Laurent
authors.initials: L
authors.lastname: Capelle
authors.forename: Karima
authors.initials: K
authors.lastname: Mokhtari
authors.forename: Yannick
authors.initials: Y
authors.lastname: Marie
authors.forename: Marc
authors.initials: M
authors.lastname: Sanson
authors.forename: Khê
authors.initials: K
authors.lastname: Hoang-Xuan
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Delattre
authors.forename: Alain
authors.initials: A
authors.lastname: Mallet
mesh_terms: D054392:Adipokines / Q000097:blood*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D001932:Brain Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000601:surgery; D000071451:Chitinase-3-Like Protein 1; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000097:blood*; D005909:Glioblastoma / Q000097:blood / Q000175:diagnosis* / Q000601:surgery; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood*; D037102:Lectins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D057234:Preoperative Period; D011379:Prognosis; D055815:Young Adult
chemical_list: D054392:Adipokines; D014408:Biomarkers, Tumor; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D005904:Glial Fibrillary Acidic Protein; C577903:IGFBP2 protein, human; D018971:Insulin-Like Growth Factor Binding Protein 2; D037102:Lectins
keywords: biomarkers; chitinase-3; glial fibrillary acidic protein (GFAP); glioblastoma multiforme; insulin-like growth factor-binding protein 2 (IGFBP-2); like protein 1 (YKL-40); plasma