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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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Relationship between mean standardized uptake value and hypoxia-inducible factor 1α or proliferating cell nuclear antigen expression in gastric cancer. (a) mRNA levels for both genes were about three-fold higher in malignant specimens than in normal mucosa (P < 0.001). (b) Spearman’s correlation analysis found no association between standardized uptake value (SUV) and proliferating cell nuclear antigen (PCNA) mRNA expression. (c) A significant correlation was found between SUV and hypoxia-inducible factor 1α (HIF1α) mRNA expression (r = 0.53, P < 0.01). Data are expressed as mean ± SEM *P < 0.05. HIF1α; Hypoxia-inducible factor 1α, PCNA; Proliferating cell nuclear antigen, SUV; Standardized Uptake Value.
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Figure 3: Relationship between mean standardized uptake value and hypoxia-inducible factor 1α or proliferating cell nuclear antigen expression in gastric cancer. (a) mRNA levels for both genes were about three-fold higher in malignant specimens than in normal mucosa (P < 0.001). (b) Spearman’s correlation analysis found no association between standardized uptake value (SUV) and proliferating cell nuclear antigen (PCNA) mRNA expression. (c) A significant correlation was found between SUV and hypoxia-inducible factor 1α (HIF1α) mRNA expression (r = 0.53, P < 0.01). Data are expressed as mean ± SEM *P < 0.05. HIF1α; Hypoxia-inducible factor 1α, PCNA; Proliferating cell nuclear antigen, SUV; Standardized Uptake Value.

Mentions: To determine whether tumor proliferation or tumor hypoxia contributes to FDG uptake, PCNA expression was analyzed as a proliferation marker and HIF1α expression as a hypoxia marker. The mRNA levels for both genes were about three-fold higher in cancerous cells than in normal mucosa (P < 0.001) (Figure 3a). To more precisely determine the association of SUV with PCNA and HIF1α mRNA expression, their correlation was quantitatively analyzed. There was no correlation between PCNA expression and SUV (Figure 3b), but HIF1α expression was correlated to SUV by Spearman’s correlation analysis (rs = 0.53, P < 0.01) (Figure 3c). There was no correlation between PCNA expression and HIF1α expression (data not shown).


[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)

Relationship between mean standardized uptake value and hypoxia-inducible factor 1α or proliferating cell nuclear antigen expression in gastric cancer. (a) mRNA levels for both genes were about three-fold higher in malignant specimens than in normal mucosa (P < 0.001). (b) Spearman’s correlation analysis found no association between standardized uptake value (SUV) and proliferating cell nuclear antigen (PCNA) mRNA expression. (c) A significant correlation was found between SUV and hypoxia-inducible factor 1α (HIF1α) mRNA expression (r = 0.53, P < 0.01). Data are expressed as mean ± SEM *P < 0.05. HIF1α; Hypoxia-inducible factor 1α, 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 3: Relationship between mean standardized uptake value and hypoxia-inducible factor 1α or proliferating cell nuclear antigen expression in gastric cancer. (a) mRNA levels for both genes were about three-fold higher in malignant specimens than in normal mucosa (P < 0.001). (b) Spearman’s correlation analysis found no association between standardized uptake value (SUV) and proliferating cell nuclear antigen (PCNA) mRNA expression. (c) A significant correlation was found between SUV and hypoxia-inducible factor 1α (HIF1α) mRNA expression (r = 0.53, P < 0.01). Data are expressed as mean ± SEM *P < 0.05. HIF1α; Hypoxia-inducible factor 1α, PCNA; Proliferating cell nuclear antigen, SUV; Standardized Uptake Value.
Mentions: To determine whether tumor proliferation or tumor hypoxia contributes to FDG uptake, PCNA expression was analyzed as a proliferation marker and HIF1α expression as a hypoxia marker. The mRNA levels for both genes were about three-fold higher in cancerous cells than in normal mucosa (P < 0.001) (Figure 3a). To more precisely determine the association of SUV with PCNA and HIF1α mRNA expression, their correlation was quantitatively analyzed. There was no correlation between PCNA expression and SUV (Figure 3b), but HIF1α expression was correlated to SUV by Spearman’s correlation analysis (rs = 0.53, P < 0.01) (Figure 3c). There was no correlation between PCNA expression and HIF1α expression (data not shown).

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