Diagnostic and prognostic value of preoperative combined GFAP, IGFBP-2, and YKL-40 plasma levels in patients with glioblastoma

Cancer. 2014 Dec 15;120(24):3972-80. doi: 10.1002/cncr.28949. Epub 2014 Aug 19.


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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines / blood*
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Brain Neoplasms / blood
  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / surgery
  • Chitinase-3-Like Protein 1
  • Female
  • Glial Fibrillary Acidic Protein / blood*
  • Glioblastoma / blood
  • Glioblastoma / diagnosis*
  • Glioblastoma / surgery
  • Humans
  • Insulin-Like Growth Factor Binding Protein 2 / blood*
  • Lectins / blood*
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Preoperative Period
  • Prognosis
  • Young Adult


  • Adipokines
  • Biomarkers, Tumor
  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1
  • Glial Fibrillary Acidic Protein
  • IGFBP2 protein, human
  • Insulin-Like Growth Factor Binding Protein 2
  • Lectins