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.).
Radiology. 2017 Sep;284(3):844-853. doi: 10.1148/radiol.2017161607. Epub 2017 Apr 6.
Purpose To determine whether fructose 1,6-bisphosphatase 1 (FBP1) expression is associated with fluorine 18 (F) fluorodeoxyglucose (FDG) accumulation in patients with hepatocellular carcinoma (HCC) and to investigate how FBP1 expression and F 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 underwent F FDG combined positron emission tomography and computed tomography (PET/CT). The relationship between maximum standardized uptake (SUV) 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. Results There was an inverse relationship between FBP1 expression and SUV (P = .003). SUV 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 FDG uptake (P = .023), and HIF1A transcriptional activity (P = .001). Conclusion SUV in patients with HCC is inversely associated with FBP1 expression, and FBP1 may inhibit F FDG uptake via the HIF1A pathway. SUV 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. RSNA, 2017.
确定果糖-1,6-二磷酸酶 1（FBP1）的表达是否与肝细胞癌（HCC）患者的氟 18（F）氟脱氧葡萄糖（FDG）摄取有关，并探讨 FBP1 表达与 FDG 摄取与肿瘤分化程度和代谢的关系，以及分子机制是否涉及缺氧诱导因子 1-α（HIF1A）转录活性。
本回顾性研究经机构审查委员会批准，并获得了患者的知情同意。85 例 HCC 患者行 FDG 正电子发射断层扫描和计算机断层扫描（PET/CT）检查。采用免疫组织化学分析方法分析最大标准化摄取值（SUV）与 FBP1、葡萄糖转运蛋白 1（GLUT1）和己糖激酶 2（HK2）表达之间的关系。在 HCC 细胞中过表达 FBP1，以研究 FBP1 在肿瘤代谢中的作用，并通过定量聚合酶链反应和荧光素酶报告基因检测研究其对 HIF1A 转录活性的影响。采用 Spearman 秩相关分析确定 FBP1 表达与 SUV 之间的相关性。
FBP1 表达与 SUV 呈负相关（P =.003）。SUV 在低分化 HCC 患者中较高（均值为 6.7±3.6[标准差]），而在高分化（均值为 2.6±0.7，P<.001）和中分化 HCC 患者中较低（均值为 4.1±2.3，P<.001）。低分化 HCC 患者的 FBP1 表达明显低于高分化（均值为 1.4±0.6，P=.006）和中分化 HCC 患者（均值为 1.2±0.2，P=.007）。在 HCC 细胞中过表达 FBP1 会导致 GLUT1 表达（P =.034）、FDG 摄取（P =.023）和 HIF1A 转录活性（P =.001）显著降低。
HCC 患者的 SUV 与 FBP1 表达呈负相关，FBP1 可能通过 HIF1A 途径抑制 FDG 摄取。SUV 在低分化 HCC 患者中较高，而在高分化和中分化 HCC 患者中较低，这可能是前者 FBP1 表达较低的结果。RSNA，2017。
