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

• Published in: Cancer Vol. 120; no. 24; pp. 3972 - 3980
• Main Authors: Gállego Pérez‐Larraya, Jaime, Paris, Sophie, Idbaih, Ahmed, Dehais, Caroline, Laigle‐Donadey, Florence, Navarro, Soledad, Capelle, Laurent, Mokhtari, Karima, Marie, Yannick, Sanson, Marc, Hoang‐Xuan, Khê, Delattre, Jean‐Yves, Mallet, Alain
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Wiley-Blackwell 15.12.2014
• Subjects: Adipokines - blood; Adult; Aged; Aged, 80 and over; Biological and medical sciences; biomarkers; Biomarkers, Tumor - blood; Brain Neoplasms - blood; Brain Neoplasms - diagnosis; Brain Neoplasms - surgery; Chitinase-3-Like Protein 1; chitinase‐3; Female; glial fibrillary acidic protein (GFAP); Glial Fibrillary Acidic Protein - blood; Glioblastoma - blood; Glioblastoma - diagnosis; Glioblastoma - surgery; glioblastoma multiforme; Humans; Insulin-Like Growth Factor Binding Protein 2 - blood; insulin‐like growth factor‐binding protein 2 (IGFBP‐2); Lectins - blood; like protein 1 (YKL‐40); Male; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neurology; plasma; Predictive Value of Tests; Preoperative Period; Prognosis; Tumors; Tumors of the nervous system. Phacomatoses; Young Adult; Chitinase; Prognosis; Biological marker; Blood plasma; Malignant glioma; Cancerology; insulin-like growth factor-binding protein 2 (IGFBP-2); chitinase-3; Secretory protein; like protein 1 (YKL-40); Diagnosis; Insulin-like growth factor binding protein 2; Human; YKL40 protein; Nervous system diseases; Enzyme; Glial fibrillary acidic protein; biomarkers; Malignant tumor; Glioblastoma multiforme; glial fibrillary acidic protein (GFAP); Glycosylases; Glycosidases; Central nervous system disease; Hydrolases; Preoperative; plasma; Cancer; glioblastoma multiforme
• ISSN: 0008-543X; 1097-0142; 1097-0142
• DOI: 10.1002/cncr.28949

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. Cancer 2014;120:3972–3980. © 2014 American Cancer Society. A combined profile of preoperative insulin‐like growth factor‐binding protein 2 (IGFBP‐2), glial fibrillary acidic protein (GFAP), and chitinase‐3‐like protein 1 (YKL‐40) plasma levels could serve as a potential diagnostic tool for patients with glioblastoma multiforme (GBM). IGFBP‐2 levels appear to constitute an independent prognostic factor in patients with GBM.