My contribution examines the fluctuations of circulating cell-free DNA (cfDNA) under the influence of physical exercise and surgical interventions, highlighting its implications for exercise physiology and clinical diagnostics. Acute physical activity induces rapid cfDNA elevations, with a return to baseline within approximately 15 minutes, a response markedly distinct from conventional markers of muscle damage and inflammation. Methylation-specific analyses, alongside observations in patients with genetic mosaics post bone marrow and liver transplantation, indicate a primary cfDNA source from neutrophils, with minor contributions from other blood cells (1). This release is modulated by the exercise's duration and intensity, presenting potential interference in liquid biopsy analyses if not preceded by 30 minutes of physical rest.
Chronic exercise patterns are associated with persistent cfDNA increases, suggesting ongoing inflammation and a continuous release-decay imbalance. This identifies cfDNA as a promising biomarker for assessing exercise-induced stress and the risk of overtraining syndrome, yet its utility in liquid biopsy for clinical diagnostics warrants further exploration.
In colorectal cancer treatment contexts, circulating tumor DNA (ctDNA) levels exhibit significant variability, likely influenced by tumor tissue blood flow and mechanical stress (2). These findings underscore the need for standardized protocols in liquid biopsy procedures, particularly concerning pre-test physical activity, to enhance the accuracy of personalized medicine approaches.
This research underscores the necessity for refined, closely monitored longitudinal studies to fully leverage liquid biopsy in personalized health monitoring, advocating for a meticulous consideration of physical and physiological factors influencing cfDNA and ctDNA dynamics.
1. Neuberger, E. W., Sontag, S., Brahmer, A., Philippi, K. F., Radsak, M. P., Wagner, W., & Simon, P. (2022). Physical activity specifically evokes release of cell-free DNA from granulocytes thereby affecting liquid biopsy. Clinical epigenetics, 14(1), 1-7.
2. Ehlert, T., Tug, S., Brahmer, A., Neef, V., Heid, F., Werner, C., ... & Simon, P. (2017). Establishing PNB-qPCR for quantifying minimal ctDNA concentrations during tumour resection. Scientific reports, 7(1), 8876.
