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

TL;DR

This paper compares blood plasma and tissue biopsy for detecting DNA methylation markers in early colorectal cancer, finding tissue biopsies more accurate but plasma tests offer a noninvasive alternative.

Contribution

The study systematically evaluates recent DNA methylation marker performance in plasma and tissue for early CRC detection, highlighting gaps in plasma-based assay accuracy.

Findings

Tissue-based samples show superior sensitivity and specificity (over 90%) for CRC detection.

Plasma-based markers like SEPT9 and HAND1 offer noninvasive detection but with lower sensitivity (40%-75.8%).

Most plasma-based assays do not meet CMS approval benchmarks for CRC screening accuracy.

Abstract

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

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

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.

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.

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.

Figures