Novel Blood-Based Biomarker Candidates in Screening for Colorectal Cancer

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Background Blood-based biomarkers could be an alternative method to increase compliance in population-based screening programs for early detection of colorectal cancer (CRC). We aimed to identify blood-based biomarkers that can identify patients with early-stage asymptomatic CRC for use in national screening programs. Materials and methods In a nested cohort of 1,982 participants with a positive fecal immunochemical test (FIT, with >100 ng Hemoglobin/mL) from the Danish CRC screening program, serum levels of 18 blood-based biomarkers (including GDF-15, hepsin, IL-8, keratin 1/10, L1CAM, MIA, MCP-1, NSE, OPG, AFP, CD44, CATD, TWEAK, YKL-40, CEA, midkine, osteonectin and ferritin) were measured. Biomarkers associated to CRC after adjusting for various possible confounders were combined with age and sex in a predictive multivariable model for CRC. Results Complete biomarker and clinical data were collected from 1,959 subjects, including 237 (12.1%) with CRC and 623 (31.8%) with advanced adenomas. IL-8 was unaffected by confounders, increased across the adenoma-carcinoma progression, and associated to CRC (OR: 1.83, 95% CI: 1.59-2.11, p < 0.01) even when restricting analyses to early-stage CRC (OR: 1.41, 95% CI: 1.15-.1.73, p<0.01). Combining IL-8, OPG, CEA, ferritin, and age resulted in an AUC of 0.717 (0.682-0.751) for discriminating subjects with and without CRC. Conclusion Application of blood-based biomarker panels consisting of colorectal neoplasia-associated proteins seem to be potential predictors for early detection of CRC. Especially IL-8 could have a significant impact on future screening models, though further testing in true screening cohorts is needed. Micro Abstract We aimed to identify blood-based biomarkers that can identify patients with early-stage asymptomatic colorectal cancer (CRC) to be used as an alternative method to increase compliance in population-based CRC screening programs. We investigated the serum levels of 18 blood-based biomarkers in a nested cohort of CRC screening participants. IL-8 was the most promising blood-based biomarker investigated, as it was unaffected by age and sex, increased across the adenoma-carcinoma progression, and associated to CRC even when restricting analyses to early-stage CRC. IL-8 could have a significant impact on future screening models where it in combination with other strong predictors such as molecular, demographic, or clinical data may contribute to a superior screening tool than fecal-based testing.

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