Journal
CLINICA CHIMICA ACTA
Volume 507, Issue -, Pages 39-53Publisher
ELSEVIER
DOI: 10.1016/j.cca.2020.03.035
Keywords
Colorectal cancer; Biomarkers; Preanalytical variation; Bowel preparation; Centrifugation; AFP; CA19-9; CEA; hs-CRP; CyFra21-1; Ferritin; Galectin-3; TIMP-1; BAG4; IL6ST; vWF; CD44; EGFR; Galectin-3 ligand; cfDNA
Categories
Funding
- Kornerup Fund
- Sven and Ina Hansen Fund
- Aage and Johanne Louis-Hansen Fund
- Aase and Ejnar Danielsen Fund
- Henrik Henriksen Fund
- Erichsen Family Fund
- Midtjyske Newspaper Fund
- US National Institutes of Health [CA152637]
- Novo Nordic Foundation [NNF17OC0025052]
- Danish Cancer Society [R133-A8520-00-S41, R146-A9466-16-S2]
- Danish Council for Strategic Research [1309-00006B]
- State of Texas Cancer Prevention Research Institute (CPRIT)
- National Institutes of Health [U01 CA68400, U01 CA152637]
- Walter and O. Kristiane Christensen Family Fund
- Foundation Juchum
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Introduction: Blood-based, cancer-associated biomarkers are susceptible to a variety of well-known preanalytical factors. The influence of bowel preparation before a diagnostic colonoscopy on biomarker levels is, however, poorly investigated. The present study assessed the influence of bowel preparation on colorectal cancer-associated biomarkers. In addition, the effect of single versus double centrifugation of plasma biomarkers was assessed. Methods: Blood samples were collected pre- and post-bowel preparation from 125 subjects scheduled for first time diagnostic colonoscopy due to symptoms attributable to CRC. The samples were separated into serum and EDTA plasma, and analyzed by four independent collaborators for: 1) the proteins AFP, CA19-9, CEA, hs-CRP, CyFra21-1, Ferritin, Galectin-3 and TIMP-1, 2) the proteins BAG4, IL6ST, vWF, CD44 and EGFR, 3) the glycoprotein Galectin-3 ligand, and 4) cell-free DNA (cfDNA). Statistical analysis of biomarker data has been performed using mixed modelling, including repeated measures. Results: The biomarkers generally showed negligible variation between pre- and post-bowel preparation except for CyFra21-1, Ferritin, BAG4 and cfDNA. CyFra21-1 levels were systematically reduced with 29% (95% CI 21-36%) by bowel preparation (p <= 0.0001). Ferritin was not significantly different between pre- and post-bowel preparation (p = 0.07), however the estimated difference (increase) was 18%. BAG4 was systematically reduced by 12% (95% CI 1-22%, p = 0.04), while cfDNA showed a significant increase of 28% (95% CI 17-39%, p < 0.0001). Double centrifugation compared to single centrifugation showed reduced vWF (ratio 0.86, p <= 0.0001) and CD44 (ratio 0.85, p = 0.016), but increased IL6ST levels (ratio 1.18, p = 0.014). Conclusions: Results of the present study demonstrated systematic, statistically significant differences between pre-bowel and post-bowel preparation levels for three independent blood-based biomarkers (BAG4, CyFra21-1, cfDNA), illustrating the importance of timing of sample collection for biomarker analyses.
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