CYP24A1 DNA Methylation in Colorectal Cancer as Potential Prognostic and Predictive Markers.

Abstract

The DNA methylation of CYP24A1 can regulate its gene expression and may play a role in the occurrence and progression of colorectal cancer (CRC). However, the association between CYP24A1 DNA methylation and the prognosis of CRC patients has not yet been reported. In this study, differential methylation analysis was conducted in both blood and tissue cohorts, and differential expression analysis was performed in the tissue cohort with in vitro validation. GO and KEGG enrichment analyses were performed on CYP24A1-related genes. A correlation between CYP24A1 promoter methylation and its gene expression was explored. Kaplan-Meier survival and Cox regression analyses were performed to investigate the impact of CYP24A1 DNA methylation on the prognosis of CRC patients. Prognostic risk scores were constructed for survival prediction. Immune infiltration analysis was also conducted. Our results showed that the hypermethylation of cg02712555 in tumor tissues (hazard ratio, 0.48; 95% confidence interval, 0.24-0.94; p = 0.032) and CpG site 41 in peripheral leukocytes (HR, 0.35; 95%CI, 0.14-0.84; p = 0.019) were both associated with decreased overall mortality in CRC patients. Prognostic risk scores showed robust predictive capabilities of these two CpG loci for the prognosis of CRC patients. CYP24A1 hypermethylation was positively correlated with infiltration levels of activated CD4 + T cells, activated CD8 + T cells, activated B cells, activated dendritic cells, and macrophages. Taken together, our findings indicate that the methylation levels of specific CpG sites within the CYP24A1 promoter region in blood leukocytes and tumors are potential prognostic and predictive markers for overall survival in CRC patients.