Biomarkers for Colorectal Cancer Detection and Screening

Colorectal cancer (CRC) remains a leading cause of cancer morbidity and mortality worldwide. Early detection through screening programmes substantially improves prognosis, yet reliance on colonoscopy and faecal immunochemical tests leaves many early-stage cases undetected. Biomarkers offer a minimally invasive alternative by analysing molecular, cellular and epigenetic signals in blood, stool or tissue. Examples include circulating tumour DNA (ctDNA) methylation patterns, circulating tumour cells (CTCs), tumour-educated platelets (TEPs) and panels of methylated genes in faecal assays. Ideal biomarkers combine high sensitivity and specificity with affordability, reproducibility and ease of use, thereby enhancing patient compliance and enabling personalised screening intervals. Recent developments have concentrated on blood-based epigenetic assays—particularly SEPT9 methylation—multi-marker panels and advanced liquid biopsy platforms. These tools not only aid early detection but also facilitate risk stratification, monitor treatment response and predict recurrence. Incorporation of validated biomarkers into routine practice has the potential to transform CRC screening, reduce reliance on invasive procedures and ultimately lower CRC-related mortality.

Research from Nature Portfolio

A comprehensive meta-analysis of the SEPT9 gene methylation assay assessed its diagnostic performance across more than 2 600 colorectal cancer cases and 6 000 controls. Three assay thresholds were compared: one positive replicate out of three (“1/3”), two out of three (“2/3”) and a single-replicate test (“1/1”). The 1/3 criterion maximised sensitivity, while the 2/3 and 1/1 approaches offered improved specificity. In symptomatic populations, the SEPT9 assay surpassed conventional serum protein markers and faecal immunochemical tests; in asymptomatic cohorts its sensitivity was lower but still significant. Findings from this study underpinned regulatory approval of the blood-based SEPT9 test and informed optimisation of epigenetic screening algorithms for broader clinical deployment.

Biomarkers for Colorectal Cancer Detection and Screening publication trend

The graph below shows the total number of articles in biomarkers for colorectal cancer detection and screening across all publications each year (not limited to Nature Index journals).

Technical terms

Biomarker: A measurable molecular or cellular indicator of disease presence, stage or progression.

Liquid biopsy: A minimally invasive test analysing tumour-derived cells or nucleic acids in body fluids.

Circulating tumour DNA (ctDNA): Fragments of DNA shed by cancer cells into the bloodstream.

Circulating tumour cells (CTCs): Intact cancer cells disseminated from a primary tumour into peripheral blood.

Tumour-educated platelets (TEPs): Platelets whose RNA profile has been altered through interaction with tumour cells.

DNA methylation assay: A technique to detect epigenetic modifications of DNA, often used to identify tumour-specific methylation patterns.

References

1. Clinical application of liquid biopsy in colorectal cancer: detection, prediction, and treatment monitoring. Molecular Cancer (2024).
2. The performance of the SEPT9 gene methylation assay and a comparison with other CRC screening tests: A meta-analysis. Scientific Reports (2017).
3. Colorectal cancer detected by liquid biopsy 2 years prior to clinical diagnosis in the HUNT study. British Journal of Cancer (2023).
4. Novel Diagnostic Biomarkers in Colorectal Cancer. International Journal of Molecular Sciences (2022).