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
Department of Sports Medicine, Rehabilitation and Disease Prevention, Johannes Gutenberg University Mainz, Mainz, Germany.
West German Proton Therapy Center Essen (WPE), University Hospital Essen, Essen, Germany.
Exp Physiol. 2025 Mar 26. 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.
循环游离DNA（cfDNA）、循环肿瘤DNA（ctDNA）和炎性细胞因子在肿瘤学中具有预后和预测价值。然而，急性运动对cfDNA水平的影响尚不清楚。在此，我们在一组癌症患者的先导队列中，与健康对照受试者相比，探讨了递增运动试验中cfDNA、ctDNA和细胞因子的动力学变化。招募实体瘤患者（n = 12）和年龄匹配的对照受试者（n = 6）进行全力心肺自行车试验。在试验前（Pre）、试验后立即（Post）和试验后90分钟（+90分钟）采集血样，检测cfDNA、ctDNA（ Kirsten大鼠肉瘤病毒癌基因同源物（KRAS）突变）、脱氧核糖核酸酶I活性和细胞因子水平。心肺运动试验在癌症患者中很容易实施，八名患者和五名对照受试者的数据可用于探索性统计评估。所有受试者的cfDNA水平从Pre到Post升高，并在+90分钟时降至基线。cfDNA浓度与脱氧核糖核酸酶I活性在对照组中明显相关，而在癌症组中不相关。中性粒细胞相关的髓过氧化物酶（MPO）、钙卫蛋白（MRP 8/14）和脂质运载蛋白A（NGAL）对运动表现出强烈反应。仅在一名癌症患者中检测到的ctDNA百分比在急性运动后下降。在我们的研究中，我们能够安全地对不同癌症类型的患者进行心肺运动试验，并随后进行生物标志物分析。我们的结果提示癌症患者中运动触发了cfDNA和中性粒细胞衍生细胞因子的释放。
