Zhang WJ, Yue KL, Wang JZ, Zhang Y. Association between heat shock factor protein 4 methylation and colorectal cancer risk and potential molecular mechanisms: A bioinformatics study. World J Gastrointest Oncol 2023; 15(12): 2150-2168 [PMID: 38173437 DOI: 10.4251/wjgo.v15.i12.2150]
Corresponding Author of This Article
Yu Zhang, MD, PhD, Associate Professor, Department of Gastroenterology, The First People’s Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, No. 157 Jinbi Road, Kunming 650032, Yunnan Province, China. yuzhang320@sina.com
Research Domain of This Article
Biochemistry & Molecular Biology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
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/
Wen-Jing Zhang, Department of Medical Oncology, The First People’s Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, Yunnan Province, China
Ke-Lin Yue, Jing-Zhai Wang, Yu Zhang, Department of Gastroenterology, The First People’s Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, Yunnan Province, China
Author contributions: Zhang WJ and Zhang Y conceived and designed the experiments; Zhang WJ, Yue KL, and Wang JZ analyzed the data; Zhang Y contributed to the data curation; Zhang WJ wrote-original draft preparation; Yue KL, Wang JZ, and Zhang Y participated in the writing-review and editing.
Supported byNational Natural Science Foundation of China, No. 82260601; Joint Foundation of Kunming Medical University and Yunnan Provincial Science and Technology Department, No. 202201AY070001-256; Grant for Clinical Medical Center of Yunnan Provincial Health Commission, No. 2021LCZXXF-XH03; and Young Academic Talents Cultivation Foundation of Yunnan Province, No. 202205AC160070.
Institutional review board statement: This study did not involve any animal and human experimentation.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
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: Yu Zhang, MD, PhD, Associate Professor, Department of Gastroenterology, The First People’s Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, No. 157 Jinbi Road, Kunming 650032, Yunnan Province, China. yuzhang320@sina.com
Received: July 28, 2023 Peer-review started: July 28, 2023 First decision: September 26, 2023 Revised: October 16, 2023 Accepted: November 17, 2023 Article in press: November 17, 2023 Published online: December 15, 2023 Processing time: 139 Days and 3.5 Hours
ARTICLE HIGHLIGHTS
Research background
DNA methylation is involved in the regulation of gene expression and has been implicated in development and outcome of colorectal cancer (CRC).
Research motivation
We previously demonstrated that heat shock factor protein 4 (HSF4) expression is abnormally high, and contributes to the malignant biological behavior of CRC in vivo and in vitro. However, the correlation of HSF4 methylation with HSF4 expression and prognosis of CRC patients, and other potential molecular mechanisms need to be further investigated.
Research objectives
The present study was proposed to investigate the correlation between HSF4 methylation and CRC risk, and to uncover the underlying molecular mechanisms.
Research methods
Identification of HSF4 methylation sites, and analysis of the differences in β values of HSF4 methylation sites and their correlation with HSF4 mRNA expression were performed using Shiny Methylation Analysis Resource Tool Web. The genes associated with HSF4 methylation were identified by LinkedOmics Web for CRC, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to reveal the functions and signaling that these associated genes may be involved in. The String database and MCODE algorithm were performed to construct protein-protein interaction (PPI) networks of HSF4 methylation-related genes.
Research results
The HSF4 gene had 19 CpG methylation sites, and their β-values were significantly higher in CRC tissues, positively correlating with HSF4 mRNA expression. The β value of the HSF4 methylation site was not associated with the prognosis of CRC patients. Notably, there are 1694 genes in CRC tissues whose expression is associated with HSF4 methylation and which are involved in immune, inflammatory, and metabolic reprogramming. EGFR, STAT3 and AXIN1 are hub genes in the PPI network constructed by these HSF4 methylation-related genes.
Research conclusions
The HSF4 gene is highly methylated in CRC, and is associated with the overexpression of HSF4 mRNA. HSF4 methylation may be involved in the process of CRC by mediating the expression of HSF4 or related genes.
Research perspectives
The finding will provide a theoretical basis and a new perspective on HSF4 as a methylation-related biomarker for future CRC diagnosis and treatment.
