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[18F]Fluorodeoxyglucose accumulation as a biological marker of hypoxic status but not glucose transport ability in gastric cancer.

Takebayashi R, Izuishi K, Yamamoto Y, Kameyama R, Mori H, Masaki T, Suzuki Y - J. Exp. Clin. Cancer Res. (2013)

Bottom Line: Tumor size was the only clinicopathological parameter that significantly correlated with SUV.When divided into intestinal and non-intestinal tumors, there was a significant correlation between SUV and tumor size in intestinal tumors.No correlation was found between SUV and mRNA expression of other genes in intestinal or non-intestinal tumors.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Gastroenterological Surgery, Kagawa University, Miki, Kita, Kagawa, Japan.

ABSTRACT

Background: The use of [18F] 2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) for detection of gastric cancer is often debated because FDG uptake varies for each patient. The purpose of this study was to clarify the molecular mechanisms involved in FDG uptake.

Material and methods: Fifty patients with gastric cancer who underwent FDG-PET and gastrectomy were studied. Snap-frozen tumor specimens were collected and examined by real-time PCR for relationships between maximum standardized uptake value (SUV) and mRNA expression of the following genes: glucose transporter 1 (GLUT1), hexokinase 2 (HK2), hypoxia-inducible factor 1α (HIF1α), and proliferating cell nuclear antigen (PCNA).

Results: Tumor size was the only clinicopathological parameter that significantly correlated with SUV. Transcripts for the genes evaluated were about three-fold higher in malignant specimens than in normal mucosa, although only HIF1α was significantly correlated with SUV. When divided into intestinal and non-intestinal tumors, there was a significant correlation between SUV and tumor size in intestinal tumors. Interestingly, the weak association between SUV and HIF1α expression in intestinal tumors was substantially stronger in non-intestinal tumors. No correlation was found between SUV and mRNA expression of other genes in intestinal or non-intestinal tumors.

Conclusion: SUV was correlated with HIF1α, but not PCNA, HK2, or GLUT1 expression. FDG accumulation could therefore represent tissue hypoxia rather than glucose transport activity for aggressive cancer growth.

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Expression of glucose metabolism-related proteins in intestinal and non-intestinal gastric cancers. Hexokinase 1 (HK1) mRNA levels were similar to those in normal mucosa, while HK2 mRNA levels were higher in both intestinal and non-intestinal gastric cancers (P < 0.01). Glucose transporter 1 (GLUT1) expression increased more in intestinal tumors than in normal mucosa (P < 0.01), but were unchanged in non-intestinal tumors. Glucose-6-phosphatase (G6Pase) expression decreased, but the difference was not significant. The mRNA expression of proliferating cell nuclear antigen (PCNA) and hypoxia-inducible factor 1α (HIF1α) increased more than three-fold compared to normal mucosa (P < 0.01). Data are expressed as mean ± SEM *P < 0.05 (ANOVA). GLUT1; Glucose transporter 1, G6Pase; Glucose-6-phosphatase, HIF1α; Hypoxia-inducible factor 1α, HK1; Hexokinase 1, HK2; Hexokinase 2, PCNA; Proliferating cell nuclear antigen, SUV; Standardized Uptake Value.
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Figure 4: Expression of glucose metabolism-related proteins in intestinal and non-intestinal gastric cancers. Hexokinase 1 (HK1) mRNA levels were similar to those in normal mucosa, while HK2 mRNA levels were higher in both intestinal and non-intestinal gastric cancers (P < 0.01). Glucose transporter 1 (GLUT1) expression increased more in intestinal tumors than in normal mucosa (P < 0.01), but were unchanged in non-intestinal tumors. Glucose-6-phosphatase (G6Pase) expression decreased, but the difference was not significant. The mRNA expression of proliferating cell nuclear antigen (PCNA) and hypoxia-inducible factor 1α (HIF1α) increased more than three-fold compared to normal mucosa (P < 0.01). Data are expressed as mean ± SEM *P < 0.05 (ANOVA). GLUT1; Glucose transporter 1, G6Pase; Glucose-6-phosphatase, HIF1α; Hypoxia-inducible factor 1α, HK1; Hexokinase 1, HK2; Hexokinase 2, PCNA; Proliferating cell nuclear antigen, SUV; Standardized Uptake Value.

Mentions: Although HK1 mRNA levels were similar, HK2 mRNA levels were higher in both specimen types compared to normal mucosa (P < 0.01). GLUT1 expression was significantly higher in intestinal specimens than in normal mucosa (P < 0.01), but was unchanged in non-intestinal specimens (Figure 4). PCNA and HIF1α expression increased three-fold in intestinal tumors (P < 0.01) compared to normal mucosa.


[18F]Fluorodeoxyglucose accumulation as a biological marker of hypoxic status but not glucose transport ability in gastric cancer.

Takebayashi R, Izuishi K, Yamamoto Y, Kameyama R, Mori H, Masaki T, Suzuki Y - J. Exp. Clin. Cancer Res. (2013)

Expression of glucose metabolism-related proteins in intestinal and non-intestinal gastric cancers. Hexokinase 1 (HK1) mRNA levels were similar to those in normal mucosa, while HK2 mRNA levels were higher in both intestinal and non-intestinal gastric cancers (P < 0.01). Glucose transporter 1 (GLUT1) expression increased more in intestinal tumors than in normal mucosa (P < 0.01), but were unchanged in non-intestinal tumors. Glucose-6-phosphatase (G6Pase) expression decreased, but the difference was not significant. The mRNA expression of proliferating cell nuclear antigen (PCNA) and hypoxia-inducible factor 1α (HIF1α) increased more than three-fold compared to normal mucosa (P < 0.01). Data are expressed as mean ± SEM *P < 0.05 (ANOVA). GLUT1; Glucose transporter 1, G6Pase; Glucose-6-phosphatase, HIF1α; Hypoxia-inducible factor 1α, HK1; Hexokinase 1, HK2; Hexokinase 2, PCNA; Proliferating cell nuclear antigen, SUV; Standardized Uptake Value.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3672048&req=5

Figure 4: Expression of glucose metabolism-related proteins in intestinal and non-intestinal gastric cancers. Hexokinase 1 (HK1) mRNA levels were similar to those in normal mucosa, while HK2 mRNA levels were higher in both intestinal and non-intestinal gastric cancers (P < 0.01). Glucose transporter 1 (GLUT1) expression increased more in intestinal tumors than in normal mucosa (P < 0.01), but were unchanged in non-intestinal tumors. Glucose-6-phosphatase (G6Pase) expression decreased, but the difference was not significant. The mRNA expression of proliferating cell nuclear antigen (PCNA) and hypoxia-inducible factor 1α (HIF1α) increased more than three-fold compared to normal mucosa (P < 0.01). Data are expressed as mean ± SEM *P < 0.05 (ANOVA). GLUT1; Glucose transporter 1, G6Pase; Glucose-6-phosphatase, HIF1α; Hypoxia-inducible factor 1α, HK1; Hexokinase 1, HK2; Hexokinase 2, PCNA; Proliferating cell nuclear antigen, SUV; Standardized Uptake Value.
Mentions: Although HK1 mRNA levels were similar, HK2 mRNA levels were higher in both specimen types compared to normal mucosa (P < 0.01). GLUT1 expression was significantly higher in intestinal specimens than in normal mucosa (P < 0.01), but was unchanged in non-intestinal specimens (Figure 4). PCNA and HIF1α expression increased three-fold in intestinal tumors (P < 0.01) compared to normal mucosa.

Bottom Line: Tumor size was the only clinicopathological parameter that significantly correlated with SUV.When divided into intestinal and non-intestinal tumors, there was a significant correlation between SUV and tumor size in intestinal tumors.No correlation was found between SUV and mRNA expression of other genes in intestinal or non-intestinal tumors.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Gastroenterological Surgery, Kagawa University, Miki, Kita, Kagawa, Japan.

ABSTRACT

Background: The use of [18F] 2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) for detection of gastric cancer is often debated because FDG uptake varies for each patient. The purpose of this study was to clarify the molecular mechanisms involved in FDG uptake.

Material and methods: Fifty patients with gastric cancer who underwent FDG-PET and gastrectomy were studied. Snap-frozen tumor specimens were collected and examined by real-time PCR for relationships between maximum standardized uptake value (SUV) and mRNA expression of the following genes: glucose transporter 1 (GLUT1), hexokinase 2 (HK2), hypoxia-inducible factor 1α (HIF1α), and proliferating cell nuclear antigen (PCNA).

Results: Tumor size was the only clinicopathological parameter that significantly correlated with SUV. Transcripts for the genes evaluated were about three-fold higher in malignant specimens than in normal mucosa, although only HIF1α was significantly correlated with SUV. When divided into intestinal and non-intestinal tumors, there was a significant correlation between SUV and tumor size in intestinal tumors. Interestingly, the weak association between SUV and HIF1α expression in intestinal tumors was substantially stronger in non-intestinal tumors. No correlation was found between SUV and mRNA expression of other genes in intestinal or non-intestinal tumors.

Conclusion: SUV was correlated with HIF1α, but not PCNA, HK2, or GLUT1 expression. FDG accumulation could therefore represent tissue hypoxia rather than glucose transport activity for aggressive cancer growth.

Show MeSH
Related in: MedlinePlus