关键词: cancer cachexia metabolomics myotubes non‐small cell lung cancer skeletal muscle wasting

来  源:   DOI:10.1111/eci.14288

Abstract:
BACKGROUND: Low physical performance is associated with higher mortality rate in multiple pathological conditions. Here, we aimed to determine whether body composition and physical performance could be prognostic factors in non-small cell lung cancer (NSCLC) patients. Moreover, we performed an exploratory approach to determine whether plasma samples from NSCLC patients could directly affect metabolic and structural phenotypes in primary muscle cells.
METHODS: This prospective cohort study included 55 metastatic NSCLC patients and seven age-matched control subjects. Assessments included physical performance, body composition, quality of life and overall survival rate. Plasma samples from a sub cohort of 18 patients were collected for exploratory studies in cell culture and metabolomic analysis.
RESULTS: We observed a higher survival rate in NSCLC patients with high performance in the timed up-and-go (+320%; p = .007), sit-to-stand (+256%; p = .01) and six-minute walking (+323%; p = .002) tests when compared to NSCLC patients with low physical performance. There was no significant association for similar analysis with body composition measurements (p > .05). Primary human myotubes incubated with plasma from NSCLC patients with low physical performance had impaired oxygen consumption rate (-54.2%; p < .0001) and cell proliferation (-44.9%; p = .007). An unbiased metabolomic analysis revealed a list of specific metabolites differentially expressed in the plasma of NSCLC patients with low physical performance.
CONCLUSIONS: These novel findings indicate that physical performance is a prognostic factor for overall survival in NSCLC patients and provide novel insights into circulating factors that could impair skeletal muscle metabolism.
摘要:
背景:在多种病理状况下,低体力表现与较高的死亡率相关。这里,我们的目的是确定身体成分和身体机能是否可能是非小细胞肺癌(NSCLC)患者的预后因素.此外,我们进行了探索性研究,以确定NSCLC患者的血浆样本是否可以直接影响原代肌细胞的代谢和结构表型.
方法:这项前瞻性队列研究包括55名转移性NSCLC患者和7名年龄匹配的对照受试者。评估包括物理性能,身体成分,生活质量和总体生存率。收集来自18名患者的亚组的血浆样品用于细胞培养和代谢组学分析的探索性研究。
结果:我们观察到非小细胞肺癌患者的生存率更高,在定时上行和上行中表现良好(+320%;p=.007),与体力表现较低的NSCLC患者相比,静坐站立(+256%;p=0.01)和六分钟步行(+323%;p=0.002)测试。类似的分析与身体成分测量没有显著关联(p>.05)。与来自具有低体力表现的NSCLC患者的血浆一起孵育的原代人肌管具有受损的耗氧率(-54.2%;p<.0001)和细胞增殖(-44.9%;p=.007)。无偏见的代谢组学分析揭示了一系列在低体力表现的NSCLC患者血浆中差异表达的特定代谢物。
结论:这些新的发现表明,身体机能是NSCLC患者总体生存的一个预后因素,并为可能损害骨骼肌代谢的循环因素提供了新的见解。
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