Maris, Calliope, D’Haene, Nicky, Trépant, Anne-Laure, Le Mercier, Marie, Sauvage, Sébastien, Allard, Justine, Rorive, Sandrine and Salmon, Isabelle (2015) IGF-IR: A new prognostic biomarker for human glioblastoma. British Journal of Cancer.

Abstract

Glioblastomas (GBMs) are the most common malignant primary brain tumors in adults. These tumors are refractory to conventional treatment approaches including surgical resection, radiotherapy and chemotherapy. The insulin-like growth factor (IGF) system is a complex network that includes soluble ligands (IGFI and IGFII), cell surface transmembrane receptors (IGF-IR and IGF-IIR), and soluble high-affinity binding proteins (IGFBP-1 to IGFBP-6). Many studies have reported a role for the IGF system in the regulation of tumor cell biology. However, the role of the different actors of this system remains unclear in GBM. The present study aimed to investigate the potential prognostic value of both the IGF ligands (IGFI and IGFII) and receptors (IGF-IR and IGF-IIR) in a large cohort of human GBMs. Tissue microarray and image analysis were conducted to quantitatively analyze the immunohistochemical expression of these proteins in 218 human GBMs. Both IGF-IR and IGF-IIR were overexpressed in GBMs compared to normal brain (p<10-4 and p=0.002, respectively). Moreover, with regard to standard clinical factors, IGF-IR positivity was identified as an independent prognostic factor associated with shorter survival (p=0.016) and was associated with a less favorable response to temozolomide. In agreement with this latter result, we showed that the IGF-IR inhibitor NVP-AEW541 enhanced in vitro the chemosensitivity of a GBM cell line (U87) to temozolomide. In conclusion, this study suggests that IGF-IR could be an interesting target for GBM therapy.

Item Type:	Article
Keywords:	glioblastoma; IGF-IR; immunohistochemistry; image analysis; biomarker; prognosis
Date Deposited:	08 Jan 2016 00:45
Last Modified:	08 Jan 2016 00:45
URI:	https://oak.novartis.com/id/eprint/9812