Evaluating plasma and tissue biopsy for DNA methylation markers in early colorectal cancer detection: a systematic review.

[BACKGROUND] DNA methylation markers are emerging as promising diagnostic tools for the early detection of colorectal cancer (CRC) that can significantly improve survival rates.

[OBJECTIVE] To compare the capabilities of blood plasma and tissue biopsy for detecting these markers in early CRC stages by diagnostic measures.

[METHODS] Nine studies published from 2020 to 2024 were analyzed, and the study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool.

[RESULTS] This review reaffirms tissue-based samples as the gold standard based on the superior sensitivity and specificity with markers such as SFMBT2 being over 90% in the 2 parameters. However, due to its invasive nature, it challenges applicability for asymptomatic patients or routine screening. Plasma-based markers (SEPT9 and HAND1) offer a noninvasive alternative, with moderate sensitivity (40%-75.8%) and high specificity (69%-94.7%), while combining multiple markers improves overall diagnostic performance. However, most plasma-based assays evaluated in this review do not yet meet the 2021 Centers for Medicare and Medicaid Services approval benchmarks of ≥74% sensitivity and ≥90% specificity compared with colonoscopy, which shows the need for further optimization before its clinical implementation. QUADAS-2 illustrated a potential high risk of bias in patient selection and flow/timing domains, which underscores the need for more standardized diagnostic workflows and assay protocols.

[CONCLUSIONS] Future research should focus on multi-marker panels, adherence to regulatory thresholds, cost-effectiveness analyses, and clear clinical management pathways to facilitate the widespread implementation of plasma-based CRC screening.