title: Fructose-1,6-Bisphosphatase 1 Reduces18F FDG Uptake in Hepatocellular Carcinoma.
abstract: Purpose To determine whether fructose 1,6-bisphosphatase 1 (FBP1) expression is associated with fluorine 18 (18F) fluorodeoxyglucose (FDG) accumulation in patients with hepatocellular carcinoma (HCC) and to investigate how FBP1 expression and18F FDG uptake are related to tumor differentiation grade and metabolism and whether the molecular mechanism involves hypoxia-inducible factor 1-α (HIF1A) transcriptional activity. Materials and Methods This retrospective study was approved by the institutional review board with informed consent. Eighty-five patients with HCC underwent18F FDG combined positron emission tomography and computed tomography (PET/CT). The relationship between maximum standardized uptake (SUVmax) 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 SUVmax. Results There was an inverse relationship between FBP1 expression and SUVmax(P = .003). SUVmaxwas 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),18F FDG uptake (P = .023), and HIF1A transcriptional activity (P = .001). Conclusion SUVmaxin patients with HCC is inversely associated with FBP1 expression, and FBP1 may inhibit18F FDG uptake via the HIF1A pathway. SUVmaxis 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.©RSNA, 2017.
authors.affiliation: From the Department of Nuclear Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Rd, Shanghai 200127, China (R.C., J. Li, X.Z., J. Liu, G.H.); Department of Cancer Metabolism, Institute of Health Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China (G.H.); and Department of Cancer Metabolism, Shanghai University of Medicine and Health Sciences, Shanghai, China (G.H.).
authors.forename: Ruohua
authors.initials: R
authors.lastname: Chen
authors.affiliation: From the Department of Nuclear Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Rd, Shanghai 200127, China (R.C., J. Li, X.Z., J. Liu, G.H.); Department of Cancer Metabolism, Institute of Health Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China (G.H.); and Department of Cancer Metabolism, Shanghai University of Medicine and Health Sciences, Shanghai, China (G.H.).
authors.forename: Jiajin
authors.initials: J
authors.lastname: Li
authors.affiliation: From the Department of Nuclear Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Rd, Shanghai 200127, China (R.C., J. Li, X.Z., J. Liu, G.H.); Department of Cancer Metabolism, Institute of Health Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China (G.H.); and Department of Cancer Metabolism, Shanghai University of Medicine and Health Sciences, Shanghai, China (G.H.).
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhou
authors.affiliation: From the Department of Nuclear Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Rd, Shanghai 200127, China (R.C., J. Li, X.Z., J. Liu, G.H.); Department of Cancer Metabolism, Institute of Health Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China (G.H.); and Department of Cancer Metabolism, Shanghai University of Medicine and Health Sciences, Shanghai, China (G.H.).
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.affiliation: From the Department of Nuclear Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Rd, Shanghai 200127, China (R.C., J. Li, X.Z., J. Liu, G.H.); Department of Cancer Metabolism, Institute of Health Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China (G.H.); and Department of Cancer Metabolism, Shanghai University of Medicine and Health Sciences, Shanghai, China (G.H.).
authors.forename: Gang
authors.initials: G
authors.lastname: Huang
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000737:chemistry / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000473:pathology; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D006597:Fructose-Bisphosphatase / Q000032:analysis / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000737:chemistry / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000072078:Positron Emission Tomography Computed Tomography; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D019788:Fluorodeoxyglucose F18; D006597:Fructose-Bisphosphatase