Assessing the exercise‐related kinetics of circulating cell‐free DNA, circulating tumour DNA, DNase I activity and cytokines in patients with solid tumours: A pilot study

• Published in: Experimental physiology
• Main Authors: Neuberger, Elmo W. I., Brahmer, Alexandra, Ehlert, Tobias, Botzenhardt, Suzan, De Falco, Alfonso, Enders, Birgit, Hähnel, Patricia S., Heintz, Achim, Schimanski, Carl C., Kindler, Thomas, Simon, Perikles
• Format: Journal Article
• Language: English
• Published: England 26.03.2025
• Subjects: cytokine; solid tumour; circulating cell‐free DNA; circulating tumour DNA; exercise; cancer; neutrophil
• ISSN: 0958-0670; 1469-445X; 1469-445X
• DOI: 10.1113/EP092167

Circulating cell‐free DNA (cfDNA), circulating tumour DNA (ctDNA) and inflammatory cytokines have prognostic and predictive value in oncology. However, the effects of acute exercise on cfDNA levels are unknown. Here, we explore the kinetics of cfDNA, ctDNA and cytokines upon an incremental exercise test in a pilot cohort of cancer patients compared with healthy control subjects. Patients with solid tumours ( n  = 12) and age‐matched control subjects ( n  = 6) were recruited to perform an all‐out cardiopulmonary bicycle test. Blood samples were collected before (Pre), directly after (Post) and 90 min after the test (+90 min), and the cfDNA, ctDNA (Kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutations), DNase I activity and cytokine levels were measured. Cardiopulmonary exercise testing was easily feasible in cancer patients, and data from eight patients and five control subjects were available for exploratory statistical evaluation. The cfDNA levels increased from Pre to Post and decreased to baseline at +90 min in all subjects. The cfDNA concentrations and DNase I activity were clearly correlated in the control but not in the cancer group. Neutrophil‐associated myeloperoxidase (MPO), calprotectin (MRP 8/14), and lipocalin A (NGAL) showed strong responses to exercise. The percentage of ctDNA, detected in only one cancer patient, decreased after acute exercise. In our study, we could safely perform cardiopulmonary exercise testing with patients with different cancer entities and subsequently run biomarker analyses. Our results hint at an exercise‐triggered release of cfDNA and neutrophil‐derived cytokines in cancer patients. What is the central question of this study? How does acute exercise affect the release and clearance of circulating cell‐free DNA in patients with solid tumours in comparison to healthy control subjects? What is the main finding and its importance? Incremental exercise immediately increases the levels of circulating cell‐free DNA and the DNase I activity in patients and control subjects. Healthy subjects show larger increases and decreases, whereas, importantly, in patients the levels normalize after 90 min of rest. Given that exercise can affect the proportion of circulating tumour DNA, our results highlight the importance of considering exercise as a preanalytical factor for cancer liquid biopsies.