Diagnostic and Prognostic Value of Preoperative Combined GFAP, IGFBP-2, and YKL-40 Plasma Levels in Patients With Glioblastoma rez-Larraya, MD, PhD1,2; Sophie Paris, MSc1; Ahmed Idbaih, MD, PhD1; Caroline Dehais, MD1; Jaime G allego Pe Florence Laigle-Donadey, MD1; Soledad Navarro, MD3; Laurent Capelle, MD3; Karima Mokhtari, MD4; Yannick Marie, MSc1; ^ Hoang-Xuan, MD, PhD1; Jean-Yves Delattre, MD1; and Alain Mallet, MD5 Marc Sanson, MD, PhD1; Khe
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 5.04). GFAP was undetectable (.1 .04 .04
Abbreviations: GBM, glioblastoma multiforme; GFAP, glial fibrillary acidic protein; IGFBP-2, insulin-like growth factor-binding protein 2; YKL-40, chitinase-3-like protein 1. a Values are expressed as the mean (standard deviation).
Plasma Protein Levels in Patients With GBM, Patients With Nonglial Tumors, and Healthy Controls
For IGFBP-2, the mean preoperative plasma levels were significantly higher in patients with GBM (435.0 pg/ mL 6 387.2 pg/mL) and in those with nonglial brain tumors (341.1 pg/mL 6 207.7 pg/mL) compared with in healthy subjects (184.0 pg/mL 6 154.6 pg/mL) (all P.10) (Fig. 1A). For YKL-40, the mean value of the preoperative plasma concentration was significantly higher in patients with GBM (76.1 ng/mL 6 61.6 ng/mL) and in patients with nonglial brain tumors (52.7 ng/mL 6 59.5 ng/mL) compared with healthy subjects (25.6 ng/mL 6 26.5 ng/ mL) (all P