Cell-free DNA in sports medicine: implications for clinical laboratory medicine

Background: Physical activity can have a strong impact on the concentration of several promising candidate biomarkers, including cell-free DNA (cfDNA). Content: This narrative review describes the current understanding of how physical strain leads to increases of cfDNA and discusses how this interferes with attempts to standardize cfDNA analysis in clinical laboratory medicine. Summary: In general, all cells of the human body can release DNA, whereas neutrophils are described as the major source releasing cfDNA under resting conditions. Event at low physical load, cfDNA is rapidly released by immune cells. We recently, identified neutrophils as the major cell-type contributing to cfDNA increases during acute exercise. Both, endurance and strength training can affect the signal-to-noise ratio of liquid biopsy (LB) analysis, affecting the clinical validity between minutes up to several days. Furthermore, we discuss why physical distress of various kinds in a perioperative cancer setting can improve or compromise signal-to-noise. Therefore, physiological events including, but not limited to, activation of blood cells can provoke pre-analytical challenges for ultra-sensitive detection of cfDNA in LB settings. Outlook: We discuss why future attempts to standardize liquid biopsy may therefore profit from a deeper understanding of the physiological release mechanisms of cfDNA.