Clinical and Translational Research
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Apr 15, 2024; 16(4): 1421-1436
Published online Apr 15, 2024. doi: 10.4251/wjgo.v16.i4.1421
NOX4 promotes tumor progression through the MAPK-MEK1/2-ERK1/2 axis in colorectal cancer
Yu-Jie Xu, Ya-Chang Huo, Qi-Tai Zhao, Jin-Yan Liu, Yi-Jun Tian, Lei-Lei Yang, Yi Zhang
Yu-Jie Xu, Ya-Chang Huo, Qi-Tai Zhao, Jin-Yan Liu, Yi-Jun Tian, Lei-Lei Yang, Yi Zhang, Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Yu-Jie Xu, Department of Oncology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou 450003, Henan Province, China
Co-first authors: Yu-Jie Xu and Ya-Chang Huo.
Author contributions: Xu YJ and Huo YC equally contributed to this work. Xu YJ, Huo YC, and Zhao QT analyzed the data; Xu YJ performed the experiments and drafted the manuscript; Huo YC and Zhao QT prepared the figures; Liu JY and Tian YJ performed hematoxylin-eosin and immunohistochemical staining experiments; Yang LL corrected the figures; Zhang Y designed, supervised and supported the study, and edited the manuscript; and all authors have read and approve the final the manuscript.
Supported by Henan Province Medical Science and Technology Research Provincial and Ministry Co-constructed Projects, No. SBGJ202101010; Major Public Welfare Projects in Henan Province, No. 201300310400; Joint Construction Project of Henan Medical Science and Technology Research Plan, No. LHGJ20220050; and Major Science and Technology Project of Henan Province, No. 221100310100.
Institutional review board statement: Approval of the research protocol by the Committee of First Affiliated Hospital of Zhengzhou University (No. 2022-KY-0828-003).
Clinical trial registration statement: This manuscript is not a Clinical Trial. The clinical part in the manuscript is a retrospective analysis. So we don’t have a clinical trial registration statement.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: All public data can be downloaded from TCGA through online database UCSC Xena (xena.ucsc.edu) and GEO using the access number: GSE17536. Other data used in the study are available from the corresponding author upon reasonable request.
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: Yi Zhang, MD, PhD, Chief Physician, Full Professor, Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou 450052, Henan Province, China. yizhang@zzu.edu.cn
Received: December 8, 2023
Peer-review started: December 8, 2023
First decision: December 21, 2023
Revised: January 4, 2024
Accepted: February 7, 2024
Article in press: February 7, 2024
Published online: April 15, 2024
Processing time: 124 Days and 12.9 Hours
ARTICLE HIGHLIGHTS
Research background

Colorectal cancer (CRC) is the leading cause of cancer-related death. Although conventional therapy has improved the prognosis of CRC, majority of patient do not well respond to these therapies. Therefore, identification of new targets is urgent for CRC.

Research motivation

Metabolic reprogramming is the major cause of therapy failure. In this study, we aim to explore the metabolic alteration in CRC tumor tissue and identify the key metabolic genes mediated this process.

Research objectives

We aim to explore the differently expressed metabolic genes between tumor and normal tissue as well as correlated with survival. In addition, we want to construct a prediction model based on this metabolic gene and identify key metabolic genes.

Research methods

We used bioinformatics analysis to identify differently expressed genes and survival related genes. Cox regression model was used to construct prediction model. Tumor biology experiments and in vivo mouse model were used to validate the role of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in mediating CRC progression.

Research results

We found that most of metabolic genes were dys-regulated between tumor and normal tissue. The NOX4 was the key metabolic gene that promoted proliferation, migration invasion and stemness of tumor cell through mitogen-activated protein kinase signaling pathway. In vivo mouse models, over-expression of NOX4 increased tumor growth and metastasis.

Research conclusions

NOX4 is a key metabolic gene that promote CRC progression.

Research perspectives

Combined therapies with targeting NOX4 may be a promising strategy for CRC treatment.