Retrospective Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 28, 2018; 24(4): 494-503
Published online Jan 28, 2018. doi: 10.3748/wjg.v24.i4.494
Low glucose metabolism in hepatocellular carcinoma with GPC3 expression
You-Cai Li, Chuan-Sheng Yang, Wen-Lan Zhou, Hong-Sheng Li, Yan-Jiang Han, Quan-Shi Wang, Hu-Bing Wu
You-Cai Li, Chuan-Sheng Yang, Wen-Lan Zhou, Hong-Sheng Li, Yan-Jiang Han, Quan-Shi Wang, Hu-Bing Wu, Nanfang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Author contributions: All authors helped to perform the research and wrote the manuscript; Han YJ contributed to the conception and design of the study; Li YC and Yang CS contributed to performing the procedures and data acquisition and analysis; Wang QS and Wu HB critically revised the manuscript for important intellectual content and approved the final version of the article to be published.
Supported by the National Natural Science Foundation of China, No. 81371591.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of the Institutional Review Board at Nanfang Hospital, Southern Medical University.
Informed consent statement: Due to the retrospective nature of the study, patients were not required to give informed consent.
Conflict-of-interest statement: All authors declare that there are no conflicts of interest to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Hu-Bing Wu, MD, Associate Professor, Nanfang PET Center, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou 510515, Guangdong Province, China. wuhbym@163.com
Telephone: +86-20-62787317 Fax: +86-20-61642127
Received: October 28, 2017
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
Abstract
AIM

To investigate the relationship between glucose metabolism and glypican-3 (GPC3) expression in hepatocellular carcinoma (HCC).

METHODS

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.

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 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).

CONCLUSION

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.

Keywords: Hepatocellular carcinoma; Glypican-3; 18F-FDG; Maximum standard uptake value; T/NT ratio; Glucose metabolism; Glucose transporter 1

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.