Xu YJ, Huo YC, Zhao QT, Liu JY, Tian YJ, Yang LL, Zhang Y. NOX4 promotes tumor progression through the MAPK-MEK1/2-ERK1/2 axis in colorectal cancer. World J Gastrointest Oncol 2024; 16(4): 1421-1436 [PMID: 38660653 DOI: 10.4251/wjgo.v16.i4.1421]
Corresponding Author of This Article
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
Research Domain of This Article
Oncology
Article-Type of This Article
Clinical and Translational Research
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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/
Apr 15, 2024 (publication date) through Feb 27, 2026
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Journal Information of This Article
Publication Name
World Journal of Gastrointestinal Oncology
ISSN
1948-5204
Publisher of This Article
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Xu YJ, Huo YC, Zhao QT, Liu JY, Tian YJ, Yang LL, Zhang Y. NOX4 promotes tumor progression through the MAPK-MEK1/2-ERK1/2 axis in colorectal cancer. World J Gastrointest Oncol 2024; 16(4): 1421-1436 [PMID: 38660653 DOI: 10.4251/wjgo.v16.i4.1421]
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 byHenan 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.
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
Core Tip
Core Tip: We first identified three clusters with different survival status based on dysregulated metabolic genes in colorectal cancer (CRC). In addition, based on differentially expressed survival-related metabolic genes, we constructed and validated a prediction model using different cohorts. Among these genes, nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) overexpression activated the mitogen-activated protein kinase-MEK1/2-ERK1/2 signaling pathway to promote cancer metastasis, whereas trametinib (a MEK1/2 inhibitor) treatment reversed this effect. Our study analyzed metabolic gene expression and highlighted the importance of NOX4 in promoting CRC metastasis, suggesting that NOX4 could be a new therapeutic target and modulating the response to clinical therapy.
