Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. May 27, 2022; 14(5): 956-971
Published online May 27, 2022. doi: 10.4254/wjh.v14.i5.956
Functions of three ubiquitin-conjugating enzyme 2 genes in hepatocellular carcinoma diagnosis and prognosis
Chun-Ye Zhang, Ming Yang
Chun-Ye Zhang, Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, United States
Ming Yang, Department of Surgery, University of Missouri, Columbia, MO 65211, United States
Author contributions: Zhang CY and Yang M conceived the idea for this study and collected and analyzed the data, wrote, finalized the manuscript letter, and contributed equally; All authors approved the submitted version and published version.
Institutional review board statement: This study was performed without animal and human studies.
Institutional animal care and use committee statement: This study was performed without animal and human studies.
Conflict-of-interest statement: Both authors declared that there was no conflict of interest with the content of this study.
Data sharing statement: All the data analyzed in this study originated from publicly available The Cancer Genome Atlas database (TCGA Research Network: https://www.cancer.gov/tcga).
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ming Yang, DVM, PhD, Postdoctoral Fellow, Department of Surgery, University of Missouri, 1030 Hitt Street, NexGen Precision Building, Room 2203, Columbia, MO 65211, United States. yangmin@health.missouri.edu
Received: December 31, 2021
Peer-review started: December 31, 2021
First decision: February 21, 2022
Revised: March 1, 2022
Accepted: May 7, 2022
Article in press: May 7, 2022
Published online: May 27, 2022
Processing time: 143 Days and 17.1 Hours
Abstract
BACKGROUND

Liver cancer ranks the third cause of cancer-related death worldwide. The most common type of liver cancer is hepatocellular carcinoma (HCC). The survival time for HCC patients is very limited by years due to the lack of efficient treatment, failure of early diagnosis, and poor prognosis. Ubiquitination plays an essential role in the biochemical processes of a variety of cellular functions.

AIM

To investigate three ubiquitination-associated genes in HCC.

METHODS

Herein, the expression levels of ubiquitin-conjugating enzymes 2 (UBE2) including UBE2C, UBE2T, and UBE2S in tumor samples of HCC patients and non-tumor controls at the Cancer Genome Atlas (TCGA) database, was comprehensively analyzed. The relationship of UBE2 gene expression level with cancer stage, prognostic outcome, and TP53 mutant status was studied.

RESULTS

Our results showed that UBE2C, UBE2T, and UBE2S genes were overexpressed in HCC samples compared to non-tumor tissues. Dependent on the cancer progression stage, three UBE2 genes showed higher expression in tumor tissues at all four stages compared to non-tumor control samples. Furthermore, a significantly higher expression of these genes was found in stage 2 and stage 3 cancers compared to stage 1 cancer. Additionally, overexpression of those genes was negatively associated with prognostic outcome and overall survival time. Patients with TP53 mutation showed a higher expression level of three UBE2 genes, indicating an association between UBE2 expression with p53 function.

CONCLUSION

In summary, this study shed light on the potential roles of UBE2C, UBE2T, UBE2S on diagnostic and prognostic biomarkers for HCC. Moreover, based on our findings, it is appealing to further explore the correlation of those genes with TP53 mutation in HCC and the related mechanisms.

Keywords: Hepatocellular carcinoma; Ubiquitin-conjugating enzyme 2; UBE2C; UBE2T; UBE2S; TP53 mutant; Biomarker; Diagnostic; Prognostics

Core Tip: Liver cancer ranks the third cause of cancer-related death worldwide. The most common type of liver cancer is hepatocellular carcinoma (HCC). Lack of effective treatment options and early diagnostic biomarkers results in a short survival time of HCC patients. Ubiquitination plays an essential role in the biochemical processes in cells. In this study, using bioinformatic analysis of the online TCGA database we found that three ubiquitin-conjugating enzyme 2 (UBE2) genes were overexpressed in HCC samples compared to normal samples in a stage-dependent manner, including UBE2C, UBE2T, and UBE2S. Additionally, overexpression of those genes was negatively associated with prognostic outcomes and overall survival times. Patients with TP53 mutation showed a higher level of expression of three UBE2 genes, indicating an association between UBE2 expression with p53 function. This study shed light on the potential roles of UBE2C, UBE2T, and UBE2S on diagnostic and prognostic biomarkers for HCC, as well as the therapeutic strategy.