BLOOD-based protein biomarkers demonstrated potential for early colorectal cancer (CRC) detection, with a multi-protein signature achieving high sensitivity for Stage I and Stage II disease and identifying advanced adenomas in a simulated screening scenario.
CRC remains a leading cause of cancer-related morbidity and mortality worldwide, although early detection can improve opportunities for intervention. Current screening approaches have limitations, including the invasive nature of colonoscopy and the limited sensitivity of faecal immunochemical tests (FIT) for advanced adenomas (AA). These challenges have prompted interest in minimally invasive blood-based biomarkers that could identify individuals with advanced colorectal neoplasia.
As part of the Horizon Europe-funded DIOPTRA project, researchers investigated circulating proteins using the Olink high-throughput proximity extension assay platform. The discovery study analysed plasma samples from 260 colonoscopy-verified participants classified as healthy, having non-advanced adenomas, having AA, or having CRC. Candidate biomarkers were identified using statistical analysis, machine learning, and multi-criteria prioritisation.
The discovery phase identified a 12-protein signature that distinguished advanced neoplasia from non-neoplastic findings. Five-fold cross-validation demonstrated 98.1% sensitivity for CRC detection and 93.1% specificity for non-advanced neoplasia. Sensitivity reached 100% for Stage I and Stage II CRC, while detection of AA achieved 50.0% sensitivity.
Researchers subsequently evaluated an expanded 17-protein signature in a multicentre validation cohort comprising 314 participants recruited across eight clinical centres, alongside 30 healthy biobank donors. Blind-test evaluation achieved 82.2% sensitivity and 89.0% specificity for non-advanced cases. Sensitivity was 94.4% for Stage I CRC and 84.5% for Stage II CRC, while AA sensitivity reached 50.2%. Specificity among healthy donors was 99.1%.
These findings suggest that blood-based protein biomarkers could support the detection of early-stage CRC and precancerous lesions, although the results reflect study-based evaluation rather than established clinical screening performance.
The researchers plan to develop multiplex immunoassays for independent validation of the identified biomarkers and assess analytical and clinical performance in a larger DIOPTRA validation cohort of 3,000 participants.
Further evaluation will be important to determine whether the protein biomarker signature can deliver reliable performance in broader screening populations. If validated, this minimally invasive approach could offer an additional option for identifying early CRC and AA, potentially addressing some limitations of existing screening methods.
Papanikolaou IS et al. Novel blood-based protein biomarker signature for early detection of colorectal cancer and advanced adenomas. Abstract OP076. UEG Congress, 17-20 October 2026.
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