Purpose: To determine whether fructose 1,6-bisphosphatase 1 (FBP1) expression is associated with fluorine 18 (F-18) fluorodeoxyglucose (FDG) accumulation in patients with hepatocellular carcinoma (HCC) and to investigate how FBP1 expression and F-18 FDG uptake are related to tumor differentiation grade and metabolism and whether the molecular mechanism involves hypoxia-inducible factor 1-alpha (HIF1A) transcriptional activity.
Materials and Methods: This retrospective study was approved by the institutional review board with informed consent. Eighty-five patients with HCC underwent 18F FDG combined positron emission tomography and computed tomography (PET/CT). The relationship between maximum standardized uptake (SUV max) and expression of FBP1, glucose transporter 1 (GLUT1), and hexokinase 2 (HK2) was analyzed with immunohistochemical analysis. In vitro FBP1 overexpression in HCC cells was used to examine the role of FBP1 in tumor metabolism, and its effect on HIF1A transcriptional activity was investigated with quantitative polymerase chain reaction and luciferase reporter assay. Spearman rank correlation was applied to determine the association between FBP1 expression and SUV max.
Results: There was an inverse relationship between FBP1 expression and SUV max (P =.003). SUV max was higher in patients with poorly differentiated HCC (mean, 6.7 +/- 3.6 [ standard deviation]) than in those with well-(mean, 2.6 +/- 0.7, P,.001) or moderately (mean, 4.1 +/- 2.3, P<.001) differentiated HCC. FBP1 expression was significantly lower in patients with poorly differentiated HCC (mean, 0.6 +/- 0.2) than in those with well-(mean, 1.4 +/- 0.6, P =.006) or moderately (mean, 1.2 +/- 0.2, P =.007) differentiated HCC. FBP1 overexpression in HCC cells led to a significant decrease in GLUT1 expression (P =.034), F-18 FDG uptake (P =.023), and HIF1A transcriptional activity (P =.001).
Conclusion: SUV max in patients with HCC is inversely associated with FBP1 expression, and FBP1 may inhibit F-18 FDG uptake via the HIF1A pathway. SUV max is higher in patients with poorly differentiated HCC than in those with well-or moderately differentiated HCC, which could be the result of lower FBP1 expression in the former. (C) RSNA, 2017
[1]Shanghai Jiao Tong Univ, Sch Med, Ren Ji Hosp, Dept Nucl Med, 1630 Dongfang Rd, Shanghai 200127, Peoples R China.
[2]Chinese Acad Sci, Inst Hlth Sci, Dept Canc Metab, Shanghai, Peoples R China.
[3]Shanghai Jiao Tong Univ, Sch Med, Shanghai, Peoples R China.
[4]Shanghai Univ Med & Hlth Sci, Dept Canc Metab, Shanghai, Peoples R China.
(8.0+极速模式)