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
ARTICLE HIGHLIGHTS
Research background

The N-Myc downstream regulatory gene (NDRG) family consists of four members (NDRG1-4), which participate in various important biological processes. However, the prognosis of NDRG family in hepatocellular carcinoma (HCC) has not been systematically evaluated yet.

Research motivation

The study revealed prognostic and potential biological role of the NDRG1, NDRG2, and NDRG3 in HCC. A prognostic risk score model with three NDRG family genes was established through multivariate Cox regression analysis and exhibited high prognostic accuracy.

Research objectives

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

Research methods

The expression of the NDRG family was downloaded from a public database. The related clinical information of HCC was downloaded from The Cancer Genome Atlas. The methylation analysis, genomic changes, and prognostic value of NDRG family were evaluated by online tools. Single sample gene set enrichment analysis was used to determine the degree of immune cell infiltration in tumors.

Research results

The expression of NDRG1 and NDRG3 in HCC was significantly higher than that in non-cancerous tissues, while the expression of NDRG2 was down regulated in HCC. The high expression of NDRG1 and NDRG3 and the low expression of NDRG2 were associated with the poor prognosis of HCC. The mutation rate of NDRG1 gene was the highest. The expression of NDRG1-3 is related to various types of filtered immune cells. Gene Ontology analysis showed that organic acid catabolism is the most important biological process related to NDRG family. Gene Set Enrichment Analysis showed that the gene sets related to metabolism, proliferation, and immunity were enriched in the high expression of NDRG1 and NDRF3 and the low expression of NDRG2.

Research conclusions

The high expression of NDRG1 and NDRG3 and the low expression of NDRG2 were significantly correlated with poor overall survival in HCC. In addition, we also established a prognostic score based on NDRG as a prognostic biomarker of overall survival in patients with HCC. Compared with NDRG1 and NDRG3, NDRG2 has a unique biological role in metabolism, which provides insights for the further study of NDRG family as a potential target of HCC.

Research perspectives

To provide preliminary suggestions for the clinical study of HCC and insights for the further study of the NDRG family as a potential target of HCC.