癌症及其治疗可能对骨骼肌造成不利影响，影响身体功能、治疗反应和生存率。然而，目前尚无研究在细胞水平上对人类患者进行了全面的长期肌肉适应性特征描述。我们在11例非小细胞肺癌（NSCLC）患者（6男/5女，平均年龄58±3岁）中研究了2个月的观察期，观察期开始于他们接受标准癌症治疗的第一个周期，同时还包括11名年龄和性别匹配的无癌症史或现患的健康对照组（HC）。我们通过对外展肌进行活体检查，评估肌纤维大小、收缩能力和线粒体含量，并评估身体功能、整体肌肉大小和功能以及循环细胞因子。NSCLC患者的体重、组成以及大腿肌肉面积和密度在观察期内未发生改变，而肌密度低于健康对照组（P=0.03）。NSCLC患者的骨骼肌纤维大小在观察期内减少了18%（所有P=0.02），并且低于健康对照组（P=0.02）。NSCLC患者的线粒体面积分数和密度在观察期内未发生变化，但是与健康对照组相比，细胞膜下和内肌纤维间百分比低于NSCLC患者（P=0.04和P=0.03）。NSCLC患者的血浆IL-6浓度、GDF-15浓度和IL-8 / CXCL8浓度较健康对照组高（HC 1.40±0.50; NSCLC 4.71±4.22；P<0.01；HC 569±166; NSCLC 2071±1168; P<0.01；HC 4.9±1.8; NSCLC 10.1±6.0; P=0.02），但是NSCLC患者的炎性标记物在观察期内没有变化。在患者中，卫星细胞激活或DNA损伤标志物未出现变化，与健康对照组相比也没有差异。患者的整体肌力在观察期内保持不变，同时单根纤维收缩能力得到改善。本研究首次全面检查了NSCLC患者骨骼肌纤维大小和功能的长期变化，并表明癌症治疗期间肌肉纤维萎缩，尽管体重稳定，一般临床测量整体和大腿肌肉大小的测量结果在此期间没有变化。© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.

Cancer and its treatment can adversely affect skeletal muscle, impacting physical function, treatment response and survival. No studies, however, have comprehensively characterized these muscle adaptations longitudinally in human patients at the cellular level.We examined skeletal muscle size and function from the whole body to the sub-cellular level in 11 patients with non-small cell lung cancer (NSCLC; 6 male/5 female, mean age 58 ± 3 years) studied over a 2-month observation period starting during their first cycle of standard of care cancer treatment and in 11 age- and sex-matched healthy controls (HC) without a current or past history of cancer. Biopsies of the vastus lateralis were performed to assess muscle fibre size, contractility and mitochondrial content, along with assessments of physical function, whole muscle size and function, and circulating cytokines.Body weight, composition and thigh muscle area and density were unaltered over time in patients with NSCLC, while muscle density was lower in patients with NSCLC versus HC (P = 0.03). Skeletal muscle fibre size decreased by 18% over time in patients (all P = 0.02) and was lower than HC (P = 0.02). Mitochondrial fractional area and density did not change over time in patients, but fractional area was lower in patients with NSCLC compared with HC (subsarcolemmal, P = 0.04; intermyofibrillar, P = 0.03). Patients with NSCLC had higher plasma concentrations of IL-6 (HC 1.40 ± 0.50; NSCLC 4.71 ± 4.22; P < 0.01), GDF-15 (HC 569 ± 166; NSCLC 2071 ± 1168; P < 0.01) and IL-8/CXCL8 (HC 4.9 ± 1.8; NSCLC 10.1 ± 6.0; P = 0.02) compared with HC, but there were no changes in inflammatory markers in patients with NSCLC over time. No changes were observed in markers of satellite cell activation or DNA damage in patients and no group differences were noted with HC. Whole-muscle strength was preserved over time in patients with NSCLC coincident with improved single fibre contractility.This study is the first to comprehensively examine longitudinal alterations in skeletal muscle fibre size and function in patients with NSCLC and suggests that muscle fibre atrophy occurs during cancer treatment despite weight stability and no changes in conventional clinical measurements of whole body or thigh muscle size over this period.© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.