Clinical and Translational Research
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Mar 6, 2022; 10(7): 2072-2086
Published online Mar 6, 2022. doi: 10.12998/wjcc.v10.i7.2072
Prognostic and biological role of the N-Myc downstream-regulated gene family in hepatocellular carcinoma
Xin Yin, Hao Yu, Xing-Kang He, Sen-Xiang Yan
Xin Yin, Hao Yu, Sen-Xiang Yan, Department of Radiation Oncology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
Xing-Kang He, Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
Author contributions: He XK and Yan SX contributed equally as corresponding authors; Yin X, Yu H, and Yan SX performed the data analysis; Yin X, Yu H, and He XK drafted the manuscript; Yin X, He XK, and Yan SX participated in study design, and data collection and analysis; He XK and Yan SX revised the manuscript; All authors read and approved the final manuscript.
Institutional review board statement: The current study does not require approval from an ethics committee.
Informed consent statement: The data that support the findings of this study are publicly available. The current study does not require signed informed consent documents.
Conflict-of-interest statement: The authors declare that there is no conflict of interest.
Data sharing statement: All data and material are public.
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: Sen-Xiang Yan, PhD, Chief Doctor, Department of Radiation Oncology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China yansenxiang@zju.edu.cn
Received: July 15, 2021
Peer-review started: July 15, 2021
First decision: September 5, 2021
Revised: September 24, 2021
Accepted: February 10, 2022
Article in press: February 10, 2022
Published online: March 6, 2022
Processing time: 229 Days and 22.6 Hours
Abstract
BACKGROUND

The N-Myc downstream-regulated gene (NDRG) family is comprised of four members (NDRG1-4) involved in various important biological processes. However, there is no systematic evaluation of the prognostic of the NDRG family in hepatocellular carcinoma (HCC).

AIM

To analyze comprehensively the biological role of the NDRG family in HCC.

METHODS

The NDRG family expression was explored using The Cancer Genome Atlas. DNA methylation interactive visualization database was used for methylation analysis of the NDRG family. The NDRG family genomic alteration was assessed using the cBioPortal. Single-sample Gene Set Enrichment Analysis was used to determine the degree of immune cell infiltration in tumors.

RESULTS

NDRG1 and NDRG3 were up-regulated in HCC, while NDRG2 was down-regulated. Consistent with expression patterns, high expression of NDRG1 and NDRG3 was associated with poor survival outcomes (P < 0.05). High expression of NDRG2 was associated with favorable survival (P < 0.005). An NDRG-based signature that statistically stratified the prognosis of the patients was constructed. The percentage of genetic alterations in the NDRG family varied from 0.3% to 11.0%, and the NDRG1 mutation rate was the highest. NDRG 1-3 expression was associated with various types of infiltrated immune cells. Gene ontology analysis revealed that organic acid catabolism was the most important biological process related to the NDRG family. Gene Set Enrichment Analysis showed that metabolic, proliferation, and immune-related gene sets were enriched during NDRG1 and NDRG3 high expression and NDRG2 low expression.

CONCLUSION

Overexpression of NDRG1 and NDRG3 and down-expression of NDRG2 are correlated with poor overall HCC prognosis. Our results may provide new insights into the indispensable role of NDRG1, 2, and 3 in the development of HCC and guide a promising new strategy for treating HCC.

Keywords: N-Myc downstream-regulated gene family; Bioinformatics; Hepatocellular carcinoma; Prognosis; Tumor-infiltrating immune cells

Core Tip: The N-Myc downstream-regulated gene (NDRG) family comprised of four members (NDRG1-4) is involved in various important biological processes. However, there is no systematic evaluation of the prognostic of the NDRG family in hepatocellular carcinoma (HCC). We aim to analyze systematically the role of the NDRG family in HCC by various bioinformatics tools. We found that NDRG1-3 may be the promising biomarker for the diagnosis and prognosis of HCC and may provide promising new targets and strategies for HCC treatment.