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±164.2ng/ml; 402.4±126ng/ml) when compared with healthy controls (301.28±73.12; 244±89.5ng/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±33.3ng/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.

Keywords: Analysis; ELISA; Gene; Glioblastoma multiforme; IGFBP-2 and IGFBP-3; Immunohistochemistry; Plasma.