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

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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:507

Enthalten in:

Clinica chimica acta; international journal of clinical chemistry - 507(2020) vom: 23. Aug., Seite 39-53

Sprache:

Englisch

Beteiligte Personen:

Lech Pedersen, Niels [VerfasserIn]
Mertz Petersen, Mathias [VerfasserIn]
Ladd, Jon J [VerfasserIn]
Lampe, Paul D [VerfasserIn]
Bresalier, Robert S [VerfasserIn]
Davis, Gerard J [VerfasserIn]
Demuth, Christina [VerfasserIn]
Jensen, Sarah Ø [VerfasserIn]
Andersen, Claus L [VerfasserIn]
Ferm, Linnea [VerfasserIn]
Christensen, Ib J [VerfasserIn]
Nielsen, Hans J [VerfasserIn]

Links:

Volltext

Themen:

AFP
BAG4
Biomarkers
Biomarkers, Tumor
Bowel preparation
CA19-9
CD44
CEA
Centrifugation
CfDNA
Colorectal cancer
CyFra21-1
EGFR
Ferritin
Galectin-3
Galectin-3 ligand
Hs-CRP
IL6ST
Journal Article
Preanalytical variation
TIMP-1
VWF

Anmerkungen:

Date Completed 13.01.2021

Date Revised 02.08.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.cca.2020.03.035

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM308573048