[HTML][HTML] Day-to-day and within-day biological variation of cell-free DNA
AT Madsen, JA Hojbjerg, BS Sorensen… - …, 2019 - thelancet.com
AT Madsen, JA Hojbjerg, BS Sorensen, A Winther-Larsen
EBioMedicine, 2019•thelancet.comBackground 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 …
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 …
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
Lęge Sofus Carl Emil Friis og hustru Olga Doris Friis' Legat, Harboefonden, and Dagmar Marshalls Fond.
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