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Day-to-day and within-day biological variation of cell-free DNA
BACKGROUND: Numerous studies have shown that cell-free DNA (cfDNA) levels may serve as a non-invasive biomarker of a broad spectrum of acute and chronic pathologies. However, in order to make clinical decisions based on cfDNA measurements, it is essential to understand the magnitude of biological va...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945267/ https://www.ncbi.nlm.nih.gov/pubmed/31648993 http://dx.doi.org/10.1016/j.ebiom.2019.10.008 |
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author | Madsen, Anne Tranberg Hojbjerg, Johanne Andersen Sorensen, Boe Sandahl Winther-Larsen, Anne |
author_facet | Madsen, Anne Tranberg Hojbjerg, Johanne Andersen Sorensen, Boe Sandahl Winther-Larsen, Anne |
author_sort | Madsen, Anne Tranberg |
collection | PubMed |
description | BACKGROUND: Numerous studies have shown that cell-free DNA (cfDNA) levels may serve as a non-invasive biomarker of a broad spectrum of acute and chronic pathologies. However, in order to make clinical decisions based on cfDNA measurements, it is essential to understand the magnitude of biological variation so this variation is not confused with a variation that actually represent a clinically relevant change. The present study was designed to evaluate the biological variation of cfDNA in healthy subjects and lung cancer patients. METHODS: Plasma samples were collected from 33 healthy subjects and ten lung cancer patients over three days, as well as during the same day. CfDNA was quantified using droplet digital PCR. Biological variation data was estimated using mixed models. FINDINGS: The within-subject variation was 25% and the between-subject variation was 30%. The reference change value for the healthy subjects was 70%. There was no systematic difference in cfDNA levels from day-to-day (p = 0⋅61), but there was a significant decline during the day (p<0⋅01). The within-subject variation in cancer patients was comparable to healthy subjects, whereas the between-subject variation was much larger (139%). No systematic differences from day-to-day were observed for the cancer patients (p>0⋅3). INTERPRETATION: Our findings show that cfDNA levels fluctuate significantly during the day and exhibit considerable within-subject variation. Thus, the data presented offer a substantial contribution to the interpretation of the clinical significance of cfDNA. FUNDING: Læge Sofus Carl Emil Friis og hustru Olga Doris Friis' Legat, Harboefonden, and Dagmar Marshalls Fond. |
format | Online Article Text |
id | pubmed-6945267 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-69452672020-01-09 Day-to-day and within-day biological variation of cell-free DNA Madsen, Anne Tranberg Hojbjerg, Johanne Andersen Sorensen, Boe Sandahl Winther-Larsen, Anne EBioMedicine Research paper BACKGROUND: Numerous studies have shown that cell-free DNA (cfDNA) levels may serve as a non-invasive biomarker of a broad spectrum of acute and chronic pathologies. However, in order to make clinical decisions based on cfDNA measurements, it is essential to understand the magnitude of biological variation so this variation is not confused with a variation that actually represent a clinically relevant change. The present study was designed to evaluate the biological variation of cfDNA in healthy subjects and lung cancer patients. METHODS: Plasma samples were collected from 33 healthy subjects and ten lung cancer patients over three days, as well as during the same day. CfDNA was quantified using droplet digital PCR. Biological variation data was estimated using mixed models. FINDINGS: The within-subject variation was 25% and the between-subject variation was 30%. The reference change value for the healthy subjects was 70%. There was no systematic difference in cfDNA levels from day-to-day (p = 0⋅61), but there was a significant decline during the day (p<0⋅01). The within-subject variation in cancer patients was comparable to healthy subjects, whereas the between-subject variation was much larger (139%). No systematic differences from day-to-day were observed for the cancer patients (p>0⋅3). INTERPRETATION: Our findings show that cfDNA levels fluctuate significantly during the day and exhibit considerable within-subject variation. Thus, the data presented offer a substantial contribution to the interpretation of the clinical significance of cfDNA. FUNDING: Læge Sofus Carl Emil Friis og hustru Olga Doris Friis' Legat, Harboefonden, and Dagmar Marshalls Fond. Elsevier 2019-10-21 /pmc/articles/PMC6945267/ /pubmed/31648993 http://dx.doi.org/10.1016/j.ebiom.2019.10.008 Text en © 2019 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research paper Madsen, Anne Tranberg Hojbjerg, Johanne Andersen Sorensen, Boe Sandahl Winther-Larsen, Anne Day-to-day and within-day biological variation of cell-free DNA |
title | Day-to-day and within-day biological variation of cell-free DNA |
title_full | Day-to-day and within-day biological variation of cell-free DNA |
title_fullStr | Day-to-day and within-day biological variation of cell-free DNA |
title_full_unstemmed | Day-to-day and within-day biological variation of cell-free DNA |
title_short | Day-to-day and within-day biological variation of cell-free DNA |
title_sort | day-to-day and within-day biological variation of cell-free dna |
topic | Research paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945267/ https://www.ncbi.nlm.nih.gov/pubmed/31648993 http://dx.doi.org/10.1016/j.ebiom.2019.10.008 |
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