Clinical colorectal cancer · 2025
Novel Blood-Based Biomarker Candidates in Screening for Colorectal Cancer.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Petersen Mathias M, Kleif Jakob, Liggett Jason, Rasmussen Morten, Jørgensen Lars N, Seidelin Jakob B, Jaensch Claudia, Vilandt Jesper, Gotschalck Kåre A, Bondeven Peter, Løve Uffe Schou, Andersen Berit, Christensen Ib J, Fritsche Herbert A, Mayer Eric, Therkildsen Christina
Аннотация
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.
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.