骨骼肌质量和线粒体氧化磷酸化水平对直肠癌患者预后的影响

The outcome effects of skeletal muscle mass and mitochondrial oxidative phosphorylation on rectal cancer patients

目的本研究旨在探讨直肠癌新辅助放化疗(NACRT)对测量体内肌肉线粒体功能和身体体质的影响。方法我们前瞻性地研究了35例完成标准化NACRT的直肠癌患者,受试者均来自于2018年3月至2019年3月期间入住我院患者。所有患者在NACRT前后均接受了心肺功能运动试验(CPET)和磷磁共振光谱分析四头肌运动后恢复情况。数据分析和报告中的患者身份及其临床过程完全保密。主要变量是两个体质测试包括评估无氧阈值时的摄氧量和运动峰值时摄氧量(m L·kg^-1·min^-1),以及一种在体内测量肌肉线粒体容量的方法—运动后磷酸肌酸恢复速率常数(min^-1)。结果患者平均年龄为67±5岁,3个主要变量在NACRT后呈显著负相关(95%CI):评估无氧阈值时摄氧量为-2.5 m L·kg^-1·min^-1(-3.7,-1.1),P=0.005;运动峰值时摄氧量为-3.9 m L·kg^-1·min^-1(-6.7,-1.1),P=0.015;和运动后磷酸肌酸(PCr)恢复速率常数为-0.4 min^-1(-0.5,-0.2),P=0.011。结论身体体质和体内肌肉线粒体功能的明显降低可能是由于肌肉线粒体的多因素机制引起,并可能影响NACRT后的体质恶化,这说明术前针对性的干预措施能提高身体体质。

Objective To investigate the effect of neoadjuvant chemoradiotherapy(NACRT)on objectively measured in vivo muscle mitochondrial function and whole-body physical fitness.Methods We prospectively studied 35 patients with rectal cancer who completed standardized neoadjuvant chemoradiotherapy,recruited from our hospital,between March 2018 and March 2019.All patients underwent a cardiopulmonary exercise test and a phosphorus magnetic resonance spectroscopy quadriceps muscle exercise-recovery study before and after neoadjuvant chemoradiotherapy.Data were analysed and reported blind to patient identity and clinical course.Primary variables of interest were the two physical fitness measures;oxygen uptake at estimated anaerobic threshold and oxygenuptake at Peak exercise(m L·kg^-1·min^-1),and the post-exercise phosphocreatine recovery rate constant(min^-1),a measure of muscle mitochondrial capacity in vivo.Result Median age was 67±9 years.Differences(95%CI)in all three primary variables were significantly negative post-NACRT:Oxygen uptake at estimated anaerobic threshold-2.5 m L·kg^-1·min^-1(-3.7,-1.1),P=0.005;Oxygen uptake at Peak-3.9 m L·kg^-1·min^-1(-6.7,-1.1),P=0.015;and postexercise phosphocreatine(PCr)recovery rate constant-0.4 min-1(-0.5,-0.2),P=0.011.Conclusions The significant decrease in both whole-body physical fitness and in vivo muscle mitochondrial function raises the possibility that muscle mitochondrial mechanisms,no doubt multifactorial,may be important in deterioration of physical fitness following neoadjuvant chemoradiotherapy.This may have implications for targeted interventions to improve physical fitness pre-surgery.