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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 transporter and glucose metabolizing enzymes in gastric cancer. (a) Glucose transporter 1 (GLUT1) staining was strong in the cell walls of tubular (a1) and poorly differentiated adenocarcinomas (a2). (b) Staining for hexokinase 2 (HK2) was seen in the cytoplasm of tubular (b1) and poorly differentiated adenocarcinomas (b2). (c) Increased mRNA expression of glucose metabolism-related proteins was observed with HK2 and GLUT1, but not HK1 and Glucose-6-phosphatase (G6Pase). (d-e) Spearman’s correlation analysis found no association between standardized uptake value (SUV) and HK2 (d) or GLUT1 (e) mRNA expression. Values are expressed as mean ± SEM. *P < 0.05. GLUT1; Glucose transporter 1, G6Pase; Glucose-6-phosphatase, HK1; Hexokinase 1, HK2; Hexokinase 2, SUV; Standardized Uptake Value.
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Figure 2: Expression of glucose transporter and glucose metabolizing enzymes in gastric cancer. (a) Glucose transporter 1 (GLUT1) staining was strong in the cell walls of tubular (a1) and poorly differentiated adenocarcinomas (a2). (b) Staining for hexokinase 2 (HK2) was seen in the cytoplasm of tubular (b1) and poorly differentiated adenocarcinomas (b2). (c) Increased mRNA expression of glucose metabolism-related proteins was observed with HK2 and GLUT1, but not HK1 and Glucose-6-phosphatase (G6Pase). (d-e) Spearman’s correlation analysis found no association between standardized uptake value (SUV) and HK2 (d) or GLUT1 (e) mRNA expression. Values are expressed as mean ± SEM. *P < 0.05. GLUT1; Glucose transporter 1, G6Pase; Glucose-6-phosphatase, HK1; Hexokinase 1, HK2; Hexokinase 2, SUV; Standardized Uptake Value.

Mentions: GLUT1 staining was seen in the cell walls, while HK2 staining was observed in the cytoplasm, of tubular (Figure 2a1, 2b1) and poorly differentiated (Figure 2a2, 2b2) adenocarcinomas. Based on these results, specimens were evaluated by qRT-PCR to determine the expression of glucose metabolism-related genes (HK1, HK2, GLUT1, and glucose-6-phosphatase (G6Pase)). HK2 and GLUT1 levels were three-fold higher in cancerous tissue than in normal mucosa (P < 0.001) (Figure 2c). G6Pase is a gluconeogenic enzyme in the liver that reverses the reaction metabolized by HK (glucose to glucose-6-phosphate) [22]. Its expression appeared to decrease in cancerous tissue, but not to a significant degree. In spite of the high levels, no significant correlation was observed between SUV and HK2 (Figure 2d) or GLUT1 (Figure 2e) expression. The glucose metabolic pathway in cancerous tissues may be too complicated to regulate with the alteration of a single molecule.


[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 transporter and glucose metabolizing enzymes in gastric cancer. (a) Glucose transporter 1 (GLUT1) staining was strong in the cell walls of tubular (a1) and poorly differentiated adenocarcinomas (a2). (b) Staining for hexokinase 2 (HK2) was seen in the cytoplasm of tubular (b1) and poorly differentiated adenocarcinomas (b2). (c) Increased mRNA expression of glucose metabolism-related proteins was observed with HK2 and GLUT1, but not HK1 and Glucose-6-phosphatase (G6Pase). (d-e) Spearman’s correlation analysis found no association between standardized uptake value (SUV) and HK2 (d) or GLUT1 (e) mRNA expression. Values are expressed as mean ± SEM. *P < 0.05. GLUT1; Glucose transporter 1, G6Pase; Glucose-6-phosphatase, HK1; Hexokinase 1, HK2; Hexokinase 2, SUV; Standardized Uptake Value.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Expression of glucose transporter and glucose metabolizing enzymes in gastric cancer. (a) Glucose transporter 1 (GLUT1) staining was strong in the cell walls of tubular (a1) and poorly differentiated adenocarcinomas (a2). (b) Staining for hexokinase 2 (HK2) was seen in the cytoplasm of tubular (b1) and poorly differentiated adenocarcinomas (b2). (c) Increased mRNA expression of glucose metabolism-related proteins was observed with HK2 and GLUT1, but not HK1 and Glucose-6-phosphatase (G6Pase). (d-e) Spearman’s correlation analysis found no association between standardized uptake value (SUV) and HK2 (d) or GLUT1 (e) mRNA expression. Values are expressed as mean ± SEM. *P < 0.05. GLUT1; Glucose transporter 1, G6Pase; Glucose-6-phosphatase, HK1; Hexokinase 1, HK2; Hexokinase 2, SUV; Standardized Uptake Value.
Mentions: GLUT1 staining was seen in the cell walls, while HK2 staining was observed in the cytoplasm, of tubular (Figure 2a1, 2b1) and poorly differentiated (Figure 2a2, 2b2) adenocarcinomas. Based on these results, specimens were evaluated by qRT-PCR to determine the expression of glucose metabolism-related genes (HK1, HK2, GLUT1, and glucose-6-phosphatase (G6Pase)). HK2 and GLUT1 levels were three-fold higher in cancerous tissue than in normal mucosa (P < 0.001) (Figure 2c). G6Pase is a gluconeogenic enzyme in the liver that reverses the reaction metabolized by HK (glucose to glucose-6-phosphate) [22]. Its expression appeared to decrease in cancerous tissue, but not to a significant degree. In spite of the high levels, no significant correlation was observed between SUV and HK2 (Figure 2d) or GLUT1 (Figure 2e) expression. The glucose metabolic pathway in cancerous tissues may be too complicated to regulate with the alteration of a single molecule.

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