Low glucose metabolism in hepatocellular carcinoma with GPC3 expression

• Published in: World journal of gastroenterology : WJG Vol. 24; no. 4; pp. 494 - 503
• Main Authors: Li, You-Cai, Yang, Chuan-Sheng, Zhou, Wen-Lan, Li, Hong-Sheng, Han, Yan-Jiang, Wang, Quan-Shi, Wu, Hu-Bing
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Inc 28.01.2018
• Subjects: Retrospective Study; Glucose metabolism; Glucose transporter 1; Hepatocellular carcinoma; Glypican-3; Maximum standard uptake value; 18F-FDG; T/NT ratio
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v24.i4.494

To investigate the relationship between glucose metabolism and glypican-3 (GPC3) expression in hepatocellular carcinoma (HCC). Immunohistochemical staining of pathological samples for GPC3 and glucose transporter 1 (GLUT1), and whole-body F-FDG PET/CT for measuring tumour glucose uptake were performed in 55 newly diagnosed HCC patients. The maximum standard uptake value (SUV ) and tumour-to-non-tumourous liver uptake (T/NT) ratio were used to quantify F-FDG uptake. F-FDG uptake assay of GPC3-expressing HepG2 and non-GPC3-expressing RH7777 cells was used to examine the effect of GPC3 in cellular glucose metabolism. The relationships between GPC3 expression and F-FDG uptake, GLUT1 expression, tumour differentiation, and other clinical indicators were analysed using Spearman rank correlation, univariate and multiple logistic regression analyses. 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 SUV (Spearman correlation coefficient = -0.281, = 0.038) and a positive relationship between GLUT1 expression and SUV (Spearman correlation coefficient = 0.681, < 0.001) in patients with HCC. Univariate analysis showed that two glucose metabolic parameters (SUV and T/NT ratio), tumour differentiation, lymph node metastasis, and TNM stage were all significantly associated with GPC3 expression ( < 0.05), whereas GLUT1 expression, sex, age, tumour size, intrahepatic lesion number, and distant metastasis showed no statistical association ( > 0.05). Further multivariate analysis revealed that only the T/N ratio was significantly correlated with GPC3 expression in patients with HCC ( < 0.05). assay revealed that the uptake of F-FDG in GPC3-expressing HepG2 cells was significantly lower than that of non-GPC3-expressing RH7777 cells ( = -20.352, < 0.001). The 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.