Abstract
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Objectives: o investigate the relationship of glucose metabolism in hepatocellular carcinomas expressing glypican-3( GPC3).
Methods: Immunohistochemical staining of samples from a hepatectomy or biopsy for GPC3 expression, glucose transporter 1 (GLUT1) expression and whole-body 18F-FDG PET/CT for measuring tumour glucose uptake were performed in 55 newly diagnosed HCC patients. The maximum standard uptake value (SUVmax) and tumor-to-non-tumorous liver uptake (T/NT) ratio were used to quantify 18F-FDG uptake. In vitro cellular 18F-FDG uptake assay of GPC3-expressing HepG2 cells and non-GPC3-expressing RH7777 cells was used to examine the effect of GPC3 in cellular glucose metabolism. The relationship between GPC3 expression and 18F-FDG uptake, GLUT1 expression, tumor differentiation and other clinical indicators were analysed using Spearman rank correlation, univariate and multiple logistic regression analyses. Results: Positive GPC3 expression was observed in 67.3% of HCC patients, including 75.0% of those with well or moderately differentiated HCC and 36.4% of those with poorly differentiated HCC. There was an inverse relationship between GPC3 expression and SUVmax (Spearman correlation coefficient=-0.281,P=0.038) and a positive relationship between GLUT1 expression and SUVmax (Spearman correlation coefficient= 0.681,P <0.001) in patients with HCC. Univariate analysis showed that two glucose metabolic parameters (SUVmax and T/NT ratio), tumour differentiation, lymph node metastasis and TNM staging were all significantly associated with GPC3 expression (all P<0.05), whereas GLUT1 expression, sex, age, tumor size, intrahepatic lesion number and distant metastasis showed no statistical association (all P>0.05). Further multivariate analysis revealed that only the T/N ratio was significantly correlated with GPC3 expression in patients with HCC (P<0.05). In vitro assay revealed that the uptake of 18F-FDG in GPC3-expressing HepG2 cells was significantly lower than that of non-GPC3-expressing RH7777 cells (t=-20.352, P<0.001).
Conclusions: Present study demonstrated that GPC3 expression is inversely associated with glucose metabolism, suggesting that GPC3 may play a role in regulating glucose metabolism in HCC.