Investigation of serum levels and tissue expression of two genes IGFBP-2 and IGFBP-3 act as potential biomarker for predicting the progression and survival in patients with glioblastoma multiforme

Abstract

Background: Identification of genetic copy number changes in glial tumors is of importance in the context of improved/refined diagnostic, prognostic procedures and therapeutic decision-making. Blood-derived biomarkers, therefore, would be useful as minimally invasive markers that could support diagnosis and enable monitoring of tumour growth and response to treatment. Objective: The aim of this study was to evaluate the clinical significance of IGFBP-2/3 in glioblastoma multiforme (GBM) and their value as predictors of survival. Methods: We examined the plasma levels of IGFBP-2 and IGFBP-3 using ELISA in patient suffering from GBM and controls groups. Furthermore, immunohistochemistry method was used to evaluate the expression levels of these markers. Results: Preoperative plasma levels of IGFBP-2 and IGFBP-3 were markedly higher in glioblastoma patients (mean +/- SD: 521.5 +/- 164.2 ng/ml; 402.4 +/- 126 ng/ml) when compared with healthy controls (301.28 +/- 73.12; 244 +/- 89.5 ng/ml; p < 0.001). Immunohistochemical results indicated that the median H score for glioblastoma tissues was higher when compared with normal tissues. The mean scores for IGFBP-2 expression in glioblastoma was higher than normal tissues (p < 0.001). Our result showed that the median H score for glioblastoma tissues was higher when compared with normal tissue for IGFBP-3 expression. The mean scores for glioblastoma tissues was higher than normal tissues (p < 0.001). We also evaluated whether plasma IGFBP-2 and IGFBP-3 levels were related to clinical features. The plasma IGFBP-2 level was strongly linked to the patient's age (R = 0.769, P = 0.001) that were strongly increased in patients with older age (>65), (mean +/- SD: 594.36 +/- 33.3 ng/ml). On the other hand, plasma IGFBP-3 level was not correlated with age (P = 0.462), sex (P = 0.532), and tumor size (P = 0.245). Our findings indicated that the tissue IGFBP-2 level was also markedly correlated with the patient's age (R = 0.612, P = 0.015). On the other hand, tissue IGFBP-3 expression level was not correlated with age (P = 0.472), sex (P = 0.512), and tumor size (P = 0.241). Kaplan-Meier survival and log-rank analysis suggested that patients with high plasma level of IGFBP-2 and tissue expression of IGFBP-2 had shorter overall survival than those with low levels (log-rank test P = 0.027; P < 0.001). Kaplan-Meier survival and log-rank analysis suggested that patients with high plasma level of IGFBP-3 and tissue expression of IGFBP-3 had shorter overall survival than those with low levels groups (log-rank test P = 0.018; P < 0.001). Conclusion: These data suggest that plasma levels and tissue levels of IGFBP-2 and IGFBP-3 may be as potential biomarkers for predicting the progression and survival in patients with GBM. (C) 2016 Elsevier B.V. All rights reserved.