TY - JOUR
T1 - Preserved muscle oxidative metabolic phenotype in newly diagnosed non-small cell lung cancer cachexia
AU - Op den Kamp, Celine M.
AU - Gosker, Harry R.
AU - Lagarde, Suzanne
AU - Tan, Daniel Y.
AU - Snepvangers, Frank J.
AU - Dingemans, Anne-Marie C.
AU - Langen, Ramon C. J.
AU - Schols, Annemie M. W. J.
PY - 2015/6
Y1 - 2015/6
N2 - Cachexia augments cancer-related mortality and has devastating effects on quality of life. Pre-clinical studies indicate that systemic inflammation-induced loss of muscle oxidative phenotype (OXPHEN) stimulates cancer-induced muscle wasting. The aim of the current proof of concept study is to validate the presence of muscle OXPHEN loss in newly diagnosed patients with lung cancer, especially in those with cachexia. Methods Quadriceps muscle biopsies of comprehensively phenotyped pre-cachectic (n=10) and cachectic (n=16) patients with non-small cell lung cancer prior to treatment were compared with healthy age-matched controls (n=22). OXPHEN was determined by assessing muscle fibre type distribution (immunohistochemistry), enzyme activity (spectrophotometry), and protein expression levels of mitochondrial complexes (western blot) as well as transcript levels of (regulatory) oxidative genes (quantitative real-time PCR). Additionally, muscle fibre cross-sectional area (immunohistochemistry) and systemic inflammation (multiplex analysis) were assessed. Results Muscle fibre cross-sectional area was smaller, and plasma levels of interleukin 6 were significantly higher in cachectic patients compared with non-cachectic patients and healthy controls. No differences in muscle fibre type distribution or oxidative and glycolytic enzyme activities were observed between the groups. Mitochondrial protein expression and gene expression levels of their regulators were also not different. Conclusion Muscle OXPHEN is preserved in newly diagnosed non-small cell lung cancer and therefore not a primary trigger of cachexia in these patients.
AB - Cachexia augments cancer-related mortality and has devastating effects on quality of life. Pre-clinical studies indicate that systemic inflammation-induced loss of muscle oxidative phenotype (OXPHEN) stimulates cancer-induced muscle wasting. The aim of the current proof of concept study is to validate the presence of muscle OXPHEN loss in newly diagnosed patients with lung cancer, especially in those with cachexia. Methods Quadriceps muscle biopsies of comprehensively phenotyped pre-cachectic (n=10) and cachectic (n=16) patients with non-small cell lung cancer prior to treatment were compared with healthy age-matched controls (n=22). OXPHEN was determined by assessing muscle fibre type distribution (immunohistochemistry), enzyme activity (spectrophotometry), and protein expression levels of mitochondrial complexes (western blot) as well as transcript levels of (regulatory) oxidative genes (quantitative real-time PCR). Additionally, muscle fibre cross-sectional area (immunohistochemistry) and systemic inflammation (multiplex analysis) were assessed. Results Muscle fibre cross-sectional area was smaller, and plasma levels of interleukin 6 were significantly higher in cachectic patients compared with non-cachectic patients and healthy controls. No differences in muscle fibre type distribution or oxidative and glycolytic enzyme activities were observed between the groups. Mitochondrial protein expression and gene expression levels of their regulators were also not different. Conclusion Muscle OXPHEN is preserved in newly diagnosed non-small cell lung cancer and therefore not a primary trigger of cachexia in these patients.
KW - Cancer cachexia
KW - Skeletal muscle
KW - Oxidative phenotype
KW - Systemic inflammation
KW - Non-small cell lung cancer
U2 - 10.1002/jcsm.12007
DO - 10.1002/jcsm.12007
M3 - Article
C2 - 26136192
SN - 2190-5991
VL - 6
SP - 164
EP - 173
JO - Journal of cachexia, sarcopenia and muscle
JF - Journal of cachexia, sarcopenia and muscle
IS - 2
ER -