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.
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).


CONCLUSIONS
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.
Department of Neurosurgery, Bou Ali Hospital, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran.
Hesam
H
Abdolhoseinpour
Department of Neurology, AJA University of Medical Sciences, Tehran, Iran.
Farzad
F
Mehrabi
Department of Ophthalmology, Alzahra Eye Hospital, Zahedan University of Medical Sciences, Zahedan, Iran.
Kourosh
K
Shahraki
Department of Neurosurgery, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Reza Jalili
RJ
Khoshnood
Department of Emergency Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Babak
B
Masoumi
Department of Molecular Biology, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Emad
E
Yahaghi
Department of Neurosurgery, AJA University of Medical Sciences, Tehran, Iran. Electronic address: Pedram_kg@yahoo.com.
Peyman Karimi
PK
Goudarzi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D001774:Blood Chemical Analysis; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D012727:Sex Characteristics; D047368:Tumor Burden
D014408:Biomarkers, Tumor; C577903:IGFBP2 protein, human; C515497:IGFBP3 protein, human; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3
Analysis; ELISA; Gene; Glioblastoma multiforme; IGFBP-2 and IGFBP-3; Immunohistochemistry; Plasma