CpG-biomarkers in tumor tissue and prediction models for the survival of colorectal cancer: A systematic review and external validation study

The research aimed to identify CpG-methylation-based prognostic biomarkers and prediction models for colorectal cancer (CRC) prognosis and validate them in a large external cohort. A systematic search was conducted, analyzing 298 unique CpGs and 12 CpG-based prognostic models from 28 studies. After adjustment for clinical variables, 48 CpGs and five prognostic models were confirmed to be associated with survival. However, the discrimination ability of the models was insufficient, with area under the receiver operating characteristic curves ranging from 0.53 to 0.62. Calibration accuracy was mostly poor, and no significant added prognostic value beyond traditional clinical variables was observed. All prognostic models were also rated at high risk of bias. While a fraction of CpGs showed potential clinical utility and generalizability, the CpG-based prognostic models performed poorly and lacked clinical relevance.