Abstract
Aim To investigate the expression of glucose transporter 3 (GLUT3) and hypoxia-inducible factor-1α protein (HIF-1α) in meningiomas and analyze the correlation between GLUT3 and HIF-1α expression with the pathological grade of peritumoral brain edema (PTBE) of meningiomas. Methods In this cross-sectional study, we analyzed meningioma specimens from 160 patients collected from January 1, 2014, to December 1, 2017, by dividing them into a low-grade (WHO I) or high-grade (WHO II and WHO III) group. Immunohistochemical analyses were used to detect the expression level of GLUT3 and HIF-1α in the tumor specimens. Results The proportion of GLUT3-positive staining in tumors sized <4 cm, 4–6 cm, and>6 cm was 35.9% (37/103), 63.6% (28/44), and 53.8% (7/13), respectively (P = 0.007). The proportion of HIF-1α-positive staining in tumors sized <4 cm, 4–6 cm, and >6 cm was 41.7% (43/103), 68.2% (30/44), and 38.5% (5/13), respectively (P = 0.010). The proportion of GLUT3-positive staining in the high-grade group and low-grade group was 70.8% (34/48) and 33.9% (38/112), respectively (P < 0.001). The proportion of HIF-1α-positive staining in the high-grade group and low-grade group was 62.5% (30/48) and 42.9% (48/112), respectively (P = 0.023). GLUT3-positive expression in meningioma PTBE grades 0, I, II, and III was 20.3% (13/64), 41.2% (14/34), 63.6% (21/33), and 82.8% (24/29), respectively (Bonferroni-corrected, P < 0.001, α/6 = 0.008). HIF-1α-positive expression in meningioma PTBE grades 0, I, II, and III was 34.4% (22/64), 47.1% (16/34), 54.5% (18/33), and 75.9% (22/29), respectively (Bonferroni-corrected, P = 0.003, α/6 = 0.008). Spearman's correlation analysis revealed a correlation between the expression of GLUT3 and HIF-1α in meningiomas (r = 0.463, P < 0.001). Multivariate analysis revealed that GLUT3-positive expression, HIF-1α-positive expression, and high pathological grade were associated with the development of PTBE (P < 0.05). Conclusions GLUT3 and HIF-1α expression in meningiomas was closely related to the tumor size, pathological grade, and PTBE. This study is the first to report a unique map-like multifocal GLUT3 staining pattern in meningiomas.
Highlights
Glucose is the main energy substrate for most eukaryotic cells
We investigated whether the expression of glucose transporter 3 (GLUT3) and Hypoxia-inducible factor-1α (HIF-1α) in meningiomas is related to the tumor size, Ki-67, peritumoral brain edema (PTBE), and pathological grade
Our study showed that cells with positive GLUT3 expression in meningiomas are separated from the intratumoral vascular network
Summary
Glucose is the main energy substrate for most eukaryotic cells. There are currently 14 known members of this family, of which GLUT3 plays a major role in glucose uptake in the brain [1]. In the case of hypoxicischemic encephalopathy, neurons can upregulate the expression of the GLUT family members, especially GLUT3 to increase tolerance to ischemia and hypoxia enabling the cells to survive and proliferate under these conditions [2]. Hypoxia-inducible factor-1α (HIF-1α) plays a crucial role in BioMed Research International the development of the tumor [3]. HIF-1α is the most important regulator of GLUT3 [4], and it can promote the “Warburg effect” where tumor cells are guaranteed a sufficient supply of energy substances under hypoxic and ischemic conditions
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