1. Development of blood-based biomarker tests for early detection of colorectal neoplasia: Influence of blood collection timing and handling procedures
- Author
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Sarah Østrup Jensen, Paul D. Lampe, Robert S. Bresalier, Linnea Ferm, Gerard J. Davis, Jon Ladd, Christina Demuth, Ib Jarle Christensen, Claus L. Andersen, Mathias M. Petersen, Hans Jørgen Nielsen, and Niels Lech Pedersen
- Subjects
Male ,0301 basic medicine ,COLONOSCOPY ,Time Factors ,Colorectal cancer ,Clinical Biochemistry ,Centrifugation ,TUMOR-MARKERS ,Biochemistry ,Gastroenterology ,RECOMMENDATIONS ,SERUM ,CEA ,0302 clinical medicine ,Blood Specimen Collection/methods ,Galectin-3 ,CD44 ,cfDNA ,Colorectal Neoplasms/blood ,Preanalytical variation ,Early Detection of Cancer ,Aged, 80 and over ,Blood Specimen Collection ,Galectin-3 ligand ,biology ,BAG4 ,General Medicine ,Middle Aged ,CA19-9 ,CANCER ,030220 oncology & carcinogenesis ,Biomarker (medicine) ,vWF ,Female ,Sample collection ,Colorectal Neoplasms ,IL6ST ,Adult ,medicine.medical_specialty ,EGFR ,AFP ,Early detection ,Article ,PANEL ,Young Adult ,03 medical and health sciences ,TIMP-1 ,Bowel preparation ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Aged ,Ferritin ,business.industry ,Biochemistry (medical) ,Repeated measures design ,TRIAGE ,CyFra21-1 ,medicine.disease ,hs-CRP ,030104 developmental biology ,Biomarkers, Tumor/blood ,BIOLOGICAL VARIATION ,biology.protein ,BIOACTIVE SUBSTANCES ,business ,Biomarkers - Abstract
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 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.
- Published
- 2020
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