运动对结直肠癌炎症、循环肿瘤细胞及循环肿瘤DNA的影响
Effects of exercise on inflammation, circulating tumor cells, and circulating tumor DNA in colorectal cancer.
作者信息
Brown Justin C, Compton Stephanie L E, Kang Andrew, Jayaraman Anjana, Gilmore L Anne, Kirby Brian J, Greenway Frank L, Yang Shengping, Spielmann Guillaume
机构信息
Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA; Louisiana State University Health Sciences Center, New Orleans School of Medicine, New Orleans, LA 70112, USA; Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA; Louisiana Cancer Research Center, New Orleans, LA 70112, USA.
Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
出版信息
J Sport Health Sci. 2025 Mar 17:101036. doi: 10.1016/j.jshs.2025.101036.
BACKGROUND
The biological mechanisms by which postdiagnosis physical activity improves disease-free survival in colorectal cancer survivors remain incompletely understood. This trial tested the hypothesis that 12 wk of moderate-intensity aerobic exercise, when compared with a control group, would change inflammation, CTCs, and ctDNA in a manner consistent with an improved cancer prognosis.
METHODS
This trial randomized Stages I-III colorectal cancer survivors to 12 wk of home-based moderate-intensity aerobic exercise or a waitlist control group. The co-primary endpoints were high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6), secondary endpoints were soluble tumor necrosis factor-α receptor 2 (sTNFαR2) and circulating tumor cells (CTCs), and the exploratory endpoint was tumor fraction quantified from circulating tumor DNA.
RESULTS
Sixty subjects were randomized (age = 60.6 ± 10.8 years, mean ± SD; 39 (65%) females; 46 (77%) colonic primary tumor), and 59 (98%) subjects completed the study. Over 12 wk, exercise adherence was 92% (95% confidence interval (95%CI): 86‒99). Exercise improved submaximal fitness capacity (0.36 metabolic equivalents; 95%CI: 0.05‒0.67; p = 0.025) and objectively measured moderate-to-vigorous-intensity physical activity (34.8%, 95%CI: 11.3‒63.1; p = 0.002) compared to control. Exercise did not change hs-CRP (20.9%, 95%CI: -17.1 to 76.2; p = 0.32), IL-6 (11.4%, 95%CI: -7.5 to 34.0; p = 0.25), or sTNFαR2 (-3.6%, 95%CI: -13.7 to 7.7; p = 0.52) compared to control. In the subgroup of subjects with elevated baseline hs-CRP (n = 35, 58.3%), aerobic exercise reduced hs-CRP (-35.5%, 95%CI: -55.3 to -3.8; p = 0.031). Exercise did not change CTCs (0.59 cells/mL, 95%CI: -0.33 to 1.51; p = 0.21) or tumor fraction (0.0005, 95%CI: -0.0024 to 0.0034; p = 0.73). In exploratory analyses, higher aerobic exercise adherence correlated with a reduction in CTCs (ρ = -0.37, 95%CI: -0.66 to -0.08; p = 0.013).
CONCLUSION
Colorectal cancer survivors achieved high adherence to a home-based moderate-intensity aerobic exercise prescription that improved fitness capacity and physical activity but did not reduce inflammation or change tumor endpoints from a liquid biopsy.
背景
诊断后进行体育活动可改善结直肠癌幸存者无病生存期的生物学机制仍未完全明确。本试验检验了以下假设：与对照组相比，12周的中等强度有氧运动能以改善癌症预后的方式改变炎症、循环肿瘤细胞（CTC）和循环肿瘤DNA（ctDNA）。
方法
本试验将I-III期结直肠癌幸存者随机分为两组，一组进行为期12周的居家中等强度有氧运动，另一组为候补对照组。共同主要终点为高敏C反应蛋白（hs-CRP）和白细胞介素-6（IL-6），次要终点为可溶性肿瘤坏死因子-α受体2（sTNFαR2）和循环肿瘤细胞（CTC），探索性终点为从循环肿瘤DNA中定量的肿瘤分数。
结果
60名受试者被随机分组（年龄=60.6±10.8岁，均值±标准差；39名（65%）为女性；46名（77%）为结肠原发性肿瘤），59名（98%）受试者完成了研究。在12周内，运动依从性为92%（95%置信区间（95%CI）：86‒99）。与对照组相比，运动改善了次最大运动能力（0.36代谢当量；95%CI：0.05‒0.67；p=0.025），且客观测量的中等至剧烈强度体育活动增加（34.8%，95%CI：11.3‒63.1；p=0.002）。与对照组相比，运动并未改变hs-CRP（20.9%，95%CI：-17.1至76.2；p=0.32）、IL-6（11.4%，95%CI：-7.5至34.0；p=0.25）或sTNFαR2（-3.6%，95%CI：-13.7至7.7；p=0.52）。在基线hs-CRP升高的受试者亚组（n=35，58.3%）中，有氧运动降低了hs-CRP（-35.5%，95%CI：-55.3至-3.8；p=0.031）。运动并未改变CTC（0.59个细胞/毫升，95%CI：-0.33至1.51；p=0.21）或肿瘤分数（0.0005，95%CI：-0.0024至0.0034；p=0.73）。在探索性分析中，更高的有氧运动依从性与CTC减少相关（ρ=-0.37，95%CI：-0.66至-0.08；p=0.013）。
结论
结直肠癌幸存者对居家中等强度有氧运动处方的依从性较高，该运动改善了运动能力和体育活动，但未减轻炎症或改变液体活检的肿瘤终点。
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