Abstract
ObjectivesTo investigate whether glioma isocitrate dehydrogenase (IDH) 1 mutation and vascular endothelial growth factor (VEGF) expression can be estimated by histogram analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).MethodsChinese Glioma Genome Atlas (CGGA) database was wined for differential expression of VEGF in gliomas with different IDH genotypes. The VEGF expression and IDH1 genotypes of 56 glioma samples in our hospital were assessed by immunohistochemistry. Preoperative DCE-MRI data of glioma samples were reviewed. Regions of interest (ROIs) covering tumor parenchyma were delineated. Histogram parameters of volume transfer constant (Ktrans) and volume of extravascular extracellular space per unit volume of tissue (Ve) derived from DCE-MRI were obtained. Histogram parameters of Ktrans, Ve and VEGF expression of IDH1 mutant type (IDH1mut) gliomas were compared with the IDH1 wildtype (IDH1wt) gliomas. Receiver operating characteristic (ROC) curve analysis was performed to differentiate IDH1mut from IDH1wt gliomas. The correlation coefficients were determined between histogram parameters of Ktrans, Ve and VEGF expression in gliomas.ResultsIn CGGA database, VEGF expression in IDHmut gliomas was lower as compared to wildtype counterpart. The immunohistochemistry of glioma samples in our hospital also confirmed the results. Comparisons demonstrated statistically significant differences in histogram parameters of Ktransand Ve [mean, standard deviation (SD), 50th, 75th, 90th. and 95th percentile] between IDH1mutand IDH1wtgliomas (P < 0.05, respectively). ROC curve analysis revealed that 50th percentile of Ktrans (0.019 min−1) and Ve (0.039) provided the perfect combination of sensitivity and specificity in differentiating gliomas with IDH1mutfrom IDH1wt. Irrespective of IDH1 mutation, histogram parameters of Ktransand Ve were correlated with VEGF expression in gliomas (P < 0.05, respectively).Conclusions VEGF expression is significantly lower in IDH1mut gliomas as compared to the wildtype counterpart, and it is non-invasively predictable with histogram analysis of DCE-MRI.
Highlights
Glioma is the most common primary intracranial tumor
In Chinese Glioma Genome Atlas (CGGA) database, Vascular endothelial growth factor (VEGF) expression in IDH mutant type (IDHmut) gliomas was lower as compared to wildtype counterpart
VEGF expression is significantly lower in IDH1 mutant type (IDH1mut) gliomas as compared to the wildtype counterpart, and it is non-invasively predictable with histogram analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)
Summary
Glioma is the most common primary intracranial tumor. According to the 2016 World Health Organization (WHO) classification criteria, mutation in the gene encoding isocitrate dehydrogenase (IDH) enzyme has been identified in the substratification of glioma [1]. A study has reported that IDH mutation inhibited PI3K/Akt signaling and reduced the HIF expression level [4]. Vascular endothelial growth factor (VEGF) regulated by HIF is one of the angiogenesis-related genes, and its over-expression correlates with poor prognoses in gliomas [5, 6]. Anti-VEGF therapy increases progression-free survival and improves quality of life in patients with glioma [7, 8]. On account of these findings, we assumed that the expression level of VEGF was lower in IDH mutant type (IDHmut) gliomas, which fitted with the indolent clinical course of IDHmut gliomas. Based on the value of DCE-MRI in gliomas and the hypothetical correlation between glioma IDH mutation and VEGF expression, we aimed to investigate whether glioma IDH1 mutation and VEGF expression can be estimated by histogram analysis of DCE-MRI
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