A panel of DNA methylation signature from peripheral blood may predict colorectal cancer susceptibility.
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, only a few studies have evaluated the predictive potential of differential DNA methylation in CRC in a prospective cohort and on a genome-wide basis. The aim of this study was to identify a potential panel of DNA methylation biomarkers in peripheral blood that is 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 the Gene Expression Omnibus (GEO) database. The differentially methylated markers were identified by moderated t-statistics. The DNA methylation panel was constructed by stepwise logistic regression and the least absolute shrinkage and selection operator in the 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, if validated be useful for the prediction of CRC risk in the future.
['Onwuka|Justina Ucheojor|JU|', 'Li|Dapeng|D|', 'Liu|Yupeng|Y|', 'Huang|Hao|H|', 'Xu|Jing|J|', 'Liu|Ying|Y|', 'Zhang|Yuanyuan|Y|', 'Zhao|Yashuang|Y|http://orcid.org/0000-0002-7425-5773']
D019540:Area Under Curve D016022:Case-Control Studies D015179:Colorectal Neoplasms D018899:CpG Islands D019175:DNA Methylation D005260:Female D005819:Genetic Markers D020022:Genetic Predisposition to Disease D006801:Humans D016015:Logistic Models D008297:Male D008875:Middle Aged D011237:Predictive Value of Tests D012307:Risk Factors
DNA methylation Peripheral blood Colorectal cancer Methylation risk score