Published online Jan 28, 2018. doi: 10.3748/wjg.v24.i4.494
Peer-review started: October 28, 2017
First decision: November 22, 20107
Revised: December 20, 2017
Accepted: December 27, 2017
Article in press: December 27, 2017
Published online: January 28, 2018
Processing time: 87 Days and 12 Hours
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 18F-FDG PET/CT for measuring tumour glucose uptake were performed in 55 newly diagnosed HCC patients. The maximum standard uptake value (SUVmax) and tumour-to-non-tumourous liver uptake (T/NT) ratio were used to quantify 18F-FDG uptake. In vitro18F-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 18F-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 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 stage were all significantly associated with GPC3 expression (P < 0.05), whereas GLUT1 expression, sex, age, tumour size, intrahepatic lesion number, and distant metastasis showed no statistical association (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).
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.
Core tip: The present study demonstrated that glypican-3 (GPC3) was positively expressed in 67.3% of hepatocellular carcinoma (HCC) patients. GPC3 expression is found to be inversely associated with the glucose metabolism of HCC tumours in the patient study. Multivariate analysis revealed that only the glucose metabolism was significantly correlated with GPC3 expression (P < 0.05), but not GLUT1 expression, tumour differentiation, or other clinical indicators (P < 0.05). Low glucose metabolism was also observed in positive GPC3-expressing HepG2 cells in cellular uptake assay. Therefore, we suggested that GPC3 may play a role in regulating glucose metabolism in HCC.