Association between heat shock factor protein 4 methylation and colorectal cancer risk and potential molecular mechanisms: A bioinformatics study.

Background: We previously demonstrated that heat shock factor protein 4 (HSF4) facilitates colorectal cancer (CRC) progression. DNA methylation, a major modifier of gene expression and stability, is involved in CRC development and outcome.

Aim: To investigate the correlation between methylation and CRC risk, and to uncover the underlying molecular mechanisms.

Methods: Differences in β values of methylation loci in multiple malignancies and their correlation with mRNA expression were analyzed based on Shiny Methylation Analysis Resource Tool. methylation-related genes were identified by LinkedOmics in CRC, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed. Protein-protein interaction network of methylation-related genes was constructed by String database and MCODE algorithm.

Results: A total of 19 CpG methylation loci were identified in , and their β values were significantly increased in CRC tissues and exhibited a positive correlation with mRNA expression. Unfortunately, the prognostic and diagnostic performance of these CpG loci in CRC patients was mediocre. In CRC, there were 1694 methylation-related genes; 1468 of which displayed positive and 226 negative associations, and they were involved in regulating phenotypes such as immune, inflammatory, and metabolic reprogramming. , , , , , and are hub genes among the methylation-related genes.

Conclusion: HSF4 is highly methylated in CRC, but there is no significant correlation between it and the prognosis and diagnosis of CRC. methylation may serve as one of the ways in which HSF4 mediates the CRC process.