A novel epigenetic signature to predict recurrence-free survival in patients with colon cancer

•Integrative analysis identified key methylation-driven genes in colon cancer.•The proposed epigenetic signature can predict the RFS for patients with colon cancer.•Nomogram provides a visual method for predicting RFS in colon cancer patients.•Joint analysis revealed that seven genes could be independent prognostic factors in colon cancer. DNA methylation plays an important role in the initiation and progression of colon cancer. The aim of the present study was to perform a comprehensive analysis of DNA methylation and gene expression profiles in order to develop a signature to predict recurrence-free survival (RFS) of colon cancer. DNA methylation and mRNA expression data were obtained from TCGA database, and were analyzed using an R package MethylMix. Functional enrichment analysis was performed on statistically significant genes identified by MethylMix criteria. The epigenetic signature and nomogram associated with the RFS of colon cancer were established by the Least Absolute Shrinkage and Selection Operator (LASSO) Cox model. Additionally, a joint survival analysis of gene expression and methylation was performed to identify potential prognostic factors for patients with colon cancer. A total of 179 differentially methylated genes were obtained using MethylMix algorithm. An epigenetic signature for RFS was developed using LASSO. Patients with high-risk had significantly worse RFS than those with low-risk. The signature is independent of clinicopathological variables and indicated better predictive power than other clinicopathological variables in patients with colon cancer. Moreover, joint survival analysis of gene expression and methylation revealed that seven methylated genes could be independent prognostic factors for RFS in colon cancer. Our proposed epigenetic signature presents potential prognostic significance in assessing recurrence risk stratification for patients with colon cancer.