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Development of blood-based biomarker tests for early detection of colorectal neoplasia: Influence of blood collection timing and handling procedures

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  1. Serological cancer-associated protein biomarker levels at bowel endoscopy: Increased risk of subsequent primary malignancy

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  2. Prognostic and Clinicopathologic Associations of LAG-3 Expression in Triple-negative Breast Cancer

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  3. Prognostic impact of histological review of high-grade endometrial carcinomas in a large Danish cohort

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  4. Detection and characterization of lung cancer using cell-free DNA fragmentomes

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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≤.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.

Original languageEnglish
JournalClinica chimica acta; international journal of clinical chemistry
Volume507
Pages (from-to)39-53
Number of pages15
ISSN0009-8981
DOIs
Publication statusPublished - Aug 2020

Bibliographical note

Copyright © 2020 Elsevier B.V. All rights reserved.

    Research areas

  • AFP, BAG4, Biomarkers, Bowel preparation, CA19-9, CD44, CEA, Centrifugation, cfDNA, Colorectal cancer, CyFra21-1, EGFR, Ferritin, Galectin-3, Galectin-3 ligand, hs-CRP, IL6ST, Preanalytical variation, TIMP-1, vWF

ID: 59657516