Gene Expression of Glucose Transporter 1 (GLUT1), Hexokinase 1 and Hexokinase 2 in Gastroenteropancreatic Neuroendocrine Tumors: Correlation with F-18-fluorodeoxyglucose Positron Emission Tomography and Cellular Proliferation

Tina Binderup; Ulrich Knigge; Birgitte Hartnack Federspiel; Peter Sommer; Jane Preuss Hasselby; Annika Loft Jakobsen; Andreas Kjær

doi:10.3390/diagnostics3040372

Gene Expression of Glucose Transporter 1 (GLUT1), Hexokinase 1 and Hexokinase 2 in Gastroenteropancreatic Neuroendocrine Tumors: Correlation with F-18-fluorodeoxyglucose Positron Emission Tomography and Cellular Proliferation

Tina Binderup, Ulrich Knigge, Birgitte Hartnack Federspiel, Peter Sommer, Jane Preuss Hasselby, Annika Loft Jakobsen, Andreas Kjær

Abstract

Neoplastic tissue exhibits high glucose utilization and over-expression of glucose transporters (GLUTs) and hexokinases (HKs), which can be imaged by¹⁸ F-Fluorodeoxyglucose-positron emission tomography (FDG-PET). The aim of the present study was to investigate the expression of glycolysis-associated genes and to compare this with FDG-PET imaging as well as with the cellular proliferation index in two cancer entities with different malignant potential. Using real-time PCR, gene expression of GLUT1, HK1 and HK2 were studied in 34 neuroendocrine tumors (NETs) in comparison with 14 colorectal adenocarcinomas (CRAs). The Ki67 proliferation index and, when available, FDG-PET imaging was compared with gene expression. Overexpression of GLUT1 gene expression was less frequent in NETs (38%) compared to CRAs (86%), P = 0.004. HK1 was overexpressed in 41% and 71% of NETs and CRAs, respectively (P = 0.111) and HK2 was overexpressed in 50% and 64% of NETs and CRAs, respectively (P = 0.53). There was a significant correlation between the Ki67 proliferation index and GLUT1 gene expression for the NETs (R = 0.34, P = 0.047), but no correlation with the hexokinases. FDG-PET identified foci in significantly fewer NETs (36%) than CRAs (86%), (P = 0.04). The gene expression results, with less frequent GLUT1 and HK1 upregulation in NETs, confirmed the lower metabolic activity of NETs compared to the more aggressive CRAs. In accordance with this, fewer NETs were FDG-PET positive compared to CRA tumors and FDG uptake correlated with GLUT1 gene expression.

Original language	English
Journal	Diagnostics
Volume	3
Issue number	4
Pages (from-to)	372-84
Number of pages	13
ISSN	2075-4418
DOIs	https://doi.org/10.3390/diagnostics3040372
Publication status	Published - Dec 2013

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Binderup, T., Knigge, U., Federspiel, B. H., Sommer, P., Hasselby, J. P., Loft Jakobsen, A., & Kjær, A. (2013). Gene Expression of Glucose Transporter 1 (GLUT1), Hexokinase 1 and Hexokinase 2 in Gastroenteropancreatic Neuroendocrine Tumors: Correlation with F-18-fluorodeoxyglucose Positron Emission Tomography and Cellular Proliferation . Diagnostics, 3(4), 372-84. https://doi.org/10.3390/diagnostics3040372

Gene Expression of Glucose Transporter 1 (GLUT1), Hexokinase 1 and Hexokinase 2 in Gastroenteropancreatic Neuroendocrine Tumors : Correlation with F-18-fluorodeoxyglucose Positron Emission Tomography and Cellular Proliferation . / Binderup, Tina ; Knigge, Ulrich; Federspiel, Birgitte Hartnack et al.

In: Diagnostics, Vol. 3, No. 4, 12.2013, p. 372-84.

Research output: Contribution to journal › Journal article › Research › peer-review

Binderup, T , Knigge, U, Federspiel, BH, Sommer, P, Hasselby, JP, Loft Jakobsen, A & Kjær, A 2013, 'Gene Expression of Glucose Transporter 1 (GLUT1), Hexokinase 1 and Hexokinase 2 in Gastroenteropancreatic Neuroendocrine Tumors: Correlation with F-18-fluorodeoxyglucose Positron Emission Tomography and Cellular Proliferation ', Diagnostics, vol. 3, no. 4, pp. 372-84. https://doi.org/10.3390/diagnostics3040372

Binderup T , Knigge U, Federspiel BH, Sommer P, Hasselby JP, Loft Jakobsen A et al. Gene Expression of Glucose Transporter 1 (GLUT1), Hexokinase 1 and Hexokinase 2 in Gastroenteropancreatic Neuroendocrine Tumors: Correlation with F-18-fluorodeoxyglucose Positron Emission Tomography and Cellular Proliferation . Diagnostics. 2013 Dec;3(4):372-84. doi: 10.3390/diagnostics3040372

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title = "Gene Expression of Glucose Transporter 1 (GLUT1), Hexokinase 1 and Hexokinase 2 in Gastroenteropancreatic Neuroendocrine Tumors: Correlation with F-18-fluorodeoxyglucose Positron Emission Tomography and Cellular Proliferation ",

abstract = "Neoplastic tissue exhibits high glucose utilization and over-expression of glucose transporters (GLUTs) and hexokinases (HKs), which can be imaged by18 F-Fluorodeoxyglucose-positron emission tomography (FDG-PET). The aim of the present study was to investigate the expression of glycolysis-associated genes and to compare this with FDG-PET imaging as well as with the cellular proliferation index in two cancer entities with different malignant potential. Using real-time PCR, gene expression of GLUT1, HK1 and HK2 were studied in 34 neuroendocrine tumors (NETs) in comparison with 14 colorectal adenocarcinomas (CRAs). The Ki67 proliferation index and, when available, FDG-PET imaging was compared with gene expression. Overexpression of GLUT1 gene expression was less frequent in NETs (38%) compared to CRAs (86%), P = 0.004. HK1 was overexpressed in 41% and 71% of NETs and CRAs, respectively (P = 0.111) and HK2 was overexpressed in 50% and 64% of NETs and CRAs, respectively (P = 0.53). There was a significant correlation between the Ki67 proliferation index and GLUT1 gene expression for the NETs (R = 0.34, P = 0.047), but no correlation with the hexokinases. FDG-PET identified foci in significantly fewer NETs (36%) than CRAs (86%), (P = 0.04). The gene expression results, with less frequent GLUT1 and HK1 upregulation in NETs, confirmed the lower metabolic activity of NETs compared to the more aggressive CRAs. In accordance with this, fewer NETs were FDG-PET positive compared to CRA tumors and FDG uptake correlated with GLUT1 gene expression.",

author = "Tina Binderup and Ulrich Knigge and Federspiel, {Birgitte Hartnack} and Peter Sommer and Hasselby, {Jane Preuss} and {Loft Jakobsen}, Annika and Andreas Kj{\ae}r",

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T2 - Correlation with F-18-fluorodeoxyglucose Positron Emission Tomography and Cellular Proliferation

AU - Binderup, Tina

AU - Knigge, Ulrich

AU - Federspiel, Birgitte Hartnack

AU - Sommer, Peter

AU - Hasselby, Jane Preuss

AU - Loft Jakobsen, Annika

AU - Kjær, Andreas

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N2 - Neoplastic tissue exhibits high glucose utilization and over-expression of glucose transporters (GLUTs) and hexokinases (HKs), which can be imaged by18 F-Fluorodeoxyglucose-positron emission tomography (FDG-PET). The aim of the present study was to investigate the expression of glycolysis-associated genes and to compare this with FDG-PET imaging as well as with the cellular proliferation index in two cancer entities with different malignant potential. Using real-time PCR, gene expression of GLUT1, HK1 and HK2 were studied in 34 neuroendocrine tumors (NETs) in comparison with 14 colorectal adenocarcinomas (CRAs). The Ki67 proliferation index and, when available, FDG-PET imaging was compared with gene expression. Overexpression of GLUT1 gene expression was less frequent in NETs (38%) compared to CRAs (86%), P = 0.004. HK1 was overexpressed in 41% and 71% of NETs and CRAs, respectively (P = 0.111) and HK2 was overexpressed in 50% and 64% of NETs and CRAs, respectively (P = 0.53). There was a significant correlation between the Ki67 proliferation index and GLUT1 gene expression for the NETs (R = 0.34, P = 0.047), but no correlation with the hexokinases. FDG-PET identified foci in significantly fewer NETs (36%) than CRAs (86%), (P = 0.04). The gene expression results, with less frequent GLUT1 and HK1 upregulation in NETs, confirmed the lower metabolic activity of NETs compared to the more aggressive CRAs. In accordance with this, fewer NETs were FDG-PET positive compared to CRA tumors and FDG uptake correlated with GLUT1 gene expression.

AB - Neoplastic tissue exhibits high glucose utilization and over-expression of glucose transporters (GLUTs) and hexokinases (HKs), which can be imaged by18 F-Fluorodeoxyglucose-positron emission tomography (FDG-PET). The aim of the present study was to investigate the expression of glycolysis-associated genes and to compare this with FDG-PET imaging as well as with the cellular proliferation index in two cancer entities with different malignant potential. Using real-time PCR, gene expression of GLUT1, HK1 and HK2 were studied in 34 neuroendocrine tumors (NETs) in comparison with 14 colorectal adenocarcinomas (CRAs). The Ki67 proliferation index and, when available, FDG-PET imaging was compared with gene expression. Overexpression of GLUT1 gene expression was less frequent in NETs (38%) compared to CRAs (86%), P = 0.004. HK1 was overexpressed in 41% and 71% of NETs and CRAs, respectively (P = 0.111) and HK2 was overexpressed in 50% and 64% of NETs and CRAs, respectively (P = 0.53). There was a significant correlation between the Ki67 proliferation index and GLUT1 gene expression for the NETs (R = 0.34, P = 0.047), but no correlation with the hexokinases. FDG-PET identified foci in significantly fewer NETs (36%) than CRAs (86%), (P = 0.04). The gene expression results, with less frequent GLUT1 and HK1 upregulation in NETs, confirmed the lower metabolic activity of NETs compared to the more aggressive CRAs. In accordance with this, fewer NETs were FDG-PET positive compared to CRA tumors and FDG uptake correlated with GLUT1 gene expression.

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JO - Diagnostics

JF - Diagnostics

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ER -