A panel of DNA methylation signature from peripheral blood may predict colorectal cancer susceptibility

Abstract

Background Differential DNA methylation panel derived from peripheral blood could serve as biomarkers of CRC susceptibility. However, most of the previous studies utilized post-diagnostic blood DNA which may be markers of disease rather than susceptibility. In addition, to date no study has evaluated the predictive potential of such markers in a prospective cohort and on a genome-wide basis. The aim of this study was to identify potential panel of DNA methylation biomarkers in peripheral blood that are associated with CRC risk and therefore serve as epigenetic biomarkers of disease susceptibility. Methods DNA methylation profile of a nested case-control study with 166 CRC and 424 healthy normal subjects were obtained from Gene Expression Omnibus (GEO) database. The differentially methylated markers were identified by moderated t-statistics. The DNA methylation panel were constructed by stepwise logistic regression and least absolute shrinkage and selection operator in training dataset. A methylation risk score (MRS) model was constructed and the association between MRS and CRC risk assessed. Results We identified 48 differentially methylated CpGs sites, of which 33 were hypomethylated. Of these, sixteen-CpG based MRS that was associated with CRC risk (OR = 2.68, 95% CI: 2.13, 3.38, P < 0.0001) was constructed. This association is confirmed in the testing dataset (OR = 2.02, 95% CI: 1.48, 2.74, P < 0.0001) and persisted in both males and females, younger and older subjects, short and long time-to-diagnosis. The MRS also predicted CRC with AUC 0.82 (95% CI: 0.76, 0.88), indicating high accuracy. Conclusions Our study has identified a novel DNA methylation panel that is associated with CRC and could be-useful for the prediction of CRC risk in the future.