Systematic Reviews
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 21, 2019; 25(23): 2947-2960
Published online Jun 21, 2019. doi: 10.3748/wjg.v25.i23.2947
Expression of genes that control core fucosylation in hepatocellular carcinoma: Systematic review
Pamela A Norton, Anand S Mehta
Pamela A Norton, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19102, United States
Anand S Mehta, Department of Cell and Molecular Pharmacology, Medical University of South Carolina, Charleston, SC 29425, United States
Author contributions: Norton PA and Mehta AS designed the research; Norton PA performed the searches; Norton PA and Mehta AS analyzed the data and wrote the paper.
Conflict-of-interest statement: The authors declare no conflicts.
PRISMA 2009 Checklist statement: This systematic review was conducted according to the PRISMA 2009 Checklist (
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:
Corresponding author: Pamela A Norton, PhD, Associate Professor, Department of Microbiology and Immunology, Drexel University College of Medicine, 245 N. 15th Street, Philadelphia, PA 19102, United States.
Telephone: +1-215-762-4146
Received: March 14, 2019
Peer-review started: March 14, 2019
First decision: April 11, 2019
Revised: April 25, 2019
Accepted: May 18, 2019
Article in press: May 18, 2019
Published online: June 21, 2019

Changes in N-linked glycosylation have been observed in the circulation of individuals with hepatocellular carcinoma. In particular, an elevation in the level of core fucosylation has been observed. However, the mechanisms through which core fucose is increased are not well understood. We hypothesized that a review of the literature and related bioinformatic review regarding six genes known to be involved in the attachment of core fucosylation, the synthesis of the fucosylation substrate guanosine diphosphate (GDP)-fucose, or the transport of the substrate into the Golgi might offer mechanistic insight into the regulation of core fucose levels.


To survey the literature to capture the involvement of genes regulating core N-linked fucosylation in hepatocellular carcinoma


The PubMed biomedical literature database was searched for the association of hepatocellular carcinoma and each of the core fucose-related genes and their protein products. We also queried The Cancer Genome Atlas Liver hepatocellular carcinoma (LIHC) dataset for genetic, epigenetic and gene expression changes for the set of six genes using the tools at cBioportal.


A total of 27 citations involving one or more of the core fucosylation-related genes (FPGT, FUK, FUT8, GMDS, SLC35C1, TSTA3) and hepatocellular carcinoma were identified. The same set of gene symbols was used to query the 371 patients with liver cancer in the LIHC dataset to identify the frequency of mRNA over or under expression, as well as non-synonymous mutations, copy number variation and methylation level. Although all six genes trended to more samples displaying over expression relative to under-expression, it was noted that a number of tumor samples had undergone amplification of the genes of the de novo synthesis pathway, GMDS (27 samples) and TSTA3 (78 samples). In contrast, the other four genes had undergone amplification in 2 or fewer samples.


Amplification of genes involved in the de novo pathway for generation of GDP-fucose, GMDS and TSTA3, likely contributes to the elevated core fucose observed in hepatocellular carcinoma.

Keywords: Liver cancer, N-linked glycosylation, Fucose, Guanosine diphosphate fucose, Hepatocellular carcinoma

Core tip: The increased level of core fucosylated N-linked glycoproteins detected in some patients with hepatocellular carcinoma may occur via several potential molecular mechanisms. We report that the genes GMDS and TSTA3, which are associated with the de novo synthesis of the fucose donor species, guanosine diphosphate fucose, can be amplified in some hepatocellular carcinoma patients. Amplification seems to be the most common genetic alteration affecting the genes that control the production of core fucosylated proteins.