Pre-cachexia in patients with stages I–III non-small cell lung cancer: Systemic inflammation and functional impairment without activation of skeletal muscle ubiquitin proteasome system

We studied if skeletal muscle NF-κB and ubiquitin proteasome system activity is increased in non-small cell lung cancer pre-cachexia

C.M. Op den Kamp


Scholarcy highlights

  • Cachexia is a prevalent phenomenon of non-small cell lung cancer which is responsible for increased mortality and deterioration of physical performance
  • To determine whether NF-κB-dependent inflammatory signaling and ubiquitin proteasome system activity were increased in NSCLC pre-cachexia, expression levels of NF-κB target genes IκBα and TNFα and E3 Ub-ligases Atrogin-1/MAFbx and muscle RING-finger protein-1 were measured in skeletal muscle
  • It is shown that there were no differences in NF-κB, UPS E3-ligase or 26S proteasome activity in pre-cachectic patients compared with healthy controls. This exploratory study shows that pre-cachexia in NSCLC is associated with significantly decreased exercise capacity without changes in body composition, and that despite the presence of systemic inflammation, no inflammatory signaling or increased UPS proteolytic activity appears appreciable in skeletal muscle
  • ], our data suggests that additional factors or prolonged exposure to systemic inflammation is required to translate systemic to local muscular inflammation in human cachexia
  • In addition to systemic and local inflammation, increased UPS-mediated proteolysis has convincingly been demonstrated in preclinical models of cancer cachexia [
  • Patients had significantly more weight loss than healthy controls but the mean observed weight loss was limited, i.e. 3.1% of premorbid body weight
  • These findings are in agreement with the absence of increased expression of Atrogin-1/MAFbx, MuRF1 and 26S proteasomal activity in the current pre-cachectic patient population with NSCLC
  • As patients in different stages of cachexia could benefit from unique intervention strategies, it is of interest to identify underlying mechanisms of the decreased exercise capacity that is already observed in non-small cell lung cancer pre-cachexia prior to muscle catabolism

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