Cancer cachexia is a major cause of patient morbidity and mortality, with no efficacious treatment or management strategy. Despite cachexia sharing pathophysiological features with a number of neuromuscular wasting conditions, including age-related sarcopenia, the mechanisms underlying cachexia remain poorly understood. Studies of related conditions suggest that pathological targeting of the neuromuscular junction (NMJ) may play a key role in cachexia, but this has yet to be investigated in human patients. Here, high-resolution morphological analyses were undertaken on NMJs of rectus abdominis obtained from patients undergoing upper GI cancer surgery compared with controls (N = 30; n = 1,165 NMJs). Cancer patients included those with cachexia and weight-stable disease. Despite the low skeletal muscle index and significant muscle fiber atrophy (P < 0.0001) in patients with cachexia, NMJ morphology was fully conserved. No significant differences were observed in any of the pre- and postsynaptic variables measured. We conclude that NMJs remain structurally intact in rectus abdominis in both cancer and cachexia, suggesting that denervation of skeletal muscle is not a major driver of pathogenesis. The absence of NMJ pathology is in stark contrast to what is found in related conditions, such as age-related sarcopenia, and supports the hypothesis that intrinsic changes within skeletal muscle, independent of any changes in motor neurons, represent the primary locus of neuromuscular pathology in cancer cachexia.

中文翻译：

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癌症恶病质患者的神经肌肉接头稳定

癌症恶病质是导致患者发病和死亡的主要原因，没有有效的治疗或管理策略。尽管恶病质与许多神经肌肉消瘦状况（包括与年龄有关的肌肉减少症）共享病理生理特征，但是对恶病质的潜在机制仍知之甚少。相关条件的研究表明，神经肌肉接头（NMJ）的病理学靶向可能在恶病质中起关键作用，但这尚未在人类患者中进行研究。在这里，对上腹部胃肠道癌手术患者获得的腹直肌的NMJs与对照组进行了高分辨率的形态学分析（N = 30；n= 1,165 NMJ）。癌症患者包括恶病质和体重稳定疾病的患者。尽管骨骼肌指数低且肌肉纤维萎缩（P<0.0001）在恶病质患者中，NMJ形态完全保守。在任何突触前和突触后变量中均未观察到显着差异。我们得出的结论是，在癌症和恶病质中，腹直肌中的NMJ仍然保持结构完整，这表明骨骼肌的神经支配不是发病机理的主要驱动力。NMJ病理学的缺乏与相关疾病（例如与年龄相关的肌肉减少症）的发现形成鲜明对比，并支持以下假设：骨骼肌内在的变化（独立于运动神经元的任何变化）代表了神经肌肉病理学的主要病因在癌症恶病质中。