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 (http://www.prisma-statement.org/).
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/
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. pan29@drexel.edu
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
ARTICLE HIGHLIGHTS
Research background

One type of protein N-linked glycosylation is the addition of fucose to the innermost core N-acetylglucosamine. Increased frequency of this modification has been associated with a number of cancers, including hepatocellular carcinoma (HCC). Systematically surveying the literature as well as performing a bioinformatics survey provided insight into what has been known about the regulation of the six genes that potentially can influence levels of core fucose.

Research motivation

Knowledge of the mechanisms whereby core fucose addition is regulated may provide information to improve the utility of this protein modification as a biomarker for detection of cancer.

Research objectives

The main objective was to survey the literature for studies that include any of the six core fucose related genes in the context of HCC. The second objective was to identify genomic alterations and gene expression changes for the same six genes in HCC.

Research methods

We searched the PubMed literature database. We performed molecular analyses on the Cancer Genome Atlas Project LIHC HCC dataset, using the tools provided by the cBioportal website (http://www.cbioportal.org/ ).

Research results

A set of 27 non-redundant citations was generated by searching for “hepatocellular carcinoma” and each of the gene symbols TSTA3, GMDS, SLC35C1 and FUT8 or their gene products. These gene products are involved in synthesis of guanosine diphosphate (GDP)-fucose, its transport into the Golgi or its attachment to N-linked glycans. No citations mentioned genes FPGT or FUK, or their gene products, along with HCC. Analyses of the 373 sample LIHC dataset revealed limited numbers of mutations affecting protein coding regions in all six genes. However, the genes TSTA3 and GMDS that encode the enzymes of the GDP-fucose de novo synthesis pathway appeared to have undergone copy number increase in 16% and 6%, respectively, of the tumor samples. Copy number increase was observed for other genes in the vicinity of those two, which lie at 8q24 and 6p25. The other four genes tended to have increased mRNA levels in a subset of samples, which did not appear to be a consequence of copy number increase.

Research conclusions

The genes that underlie core fucose generation are not well studied in the context of HCC. Multiple molecular mechanisms appear to account for the increase in core fucosylated glycoproteins observed in some patients with HCC, with chromosomal amplification being most common.

Research perspectives

Future studies will be needed to assess whether the results observed with the LIHC dataset will be generalizable to other patient populations.