Novel Blood-Based Biomarker Candidates in Screening for Colorectal Cancer.

[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 1982 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 1959 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 < .01) even when restricting analyses to early-stage CRC (OR: 1.41, 95% CI, 1.15-1.73, P < .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.