Published online Dec 15, 2023. doi: 10.4251/wjgo.v15.i12.2150
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
DNA methylation is involved in the regulation of gene expression and has been implicated in development and outcome of colorectal cancer (CRC).
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.
The present study was proposed to investigate the correlation between HSF4 methylation and CRC risk, and to uncover the underlying molecular mechanisms.
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.
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.
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.
The finding will provide a theoretical basis and a new perspective on HSF4 as a methylation-related biomarker for future CRC diagnosis and treatment.