Abstract
In CRC, screening compliance is decreased due to the experienced discomfort associated with colonoscopy, although this method is the gold standard in terms of sensitivity and specificity. Promoter DNA methylation (hypomethylation or hypermethylation) has been linked to all CRC stages. Study objectives: to systematically review the current knowledge on approved biomarkers, reveal new potential ones, and inspect tactics that can improve performance. This research was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines; the risk of bias was evaluated using the revised Quality Assessment of Diagnostic Accuracy Studies criteria (QUADAS-2). The Web of Science(®) Core Collection, MEDLINE(®) and Scopus(®) databases were searched for original articles published in peer-reviewed journals with the specific keywords "colorectal cancer", "early detection", "early-stage colorectal cancer", "epigenetics", "biomarkers", "DNA methylation biomarkers", "stool or blood or tissue or biopsy", "NDRG4", "BMP3", "SEPT9", and "SDC2". Based on eligibility criteria, 74 articles were accepted for analysis. mSDC2 and mSEPT9 were frequently assessed in studies, alone or together as part of the ColoDefense panel test-the latter with the greatest performance. mBMP3 may not be an appropriate marker for detecting CRC. A panel of five methylated binding sites of the CTCF gene holds the promise for early-stage specific detection of CRC. CRC screening compliance and accuracy can be enhanced by employing a stool mt-DNA methylation test.