Preserved muscle oxidative metabolic phenotype in newly diagnosed non-small cell lung cancer patients

Abstract

Cachexia has devastating effects on quality of life and augments cancer-related mortality. Preclinical studies indicate that systemic inflammation-induced loss of muscle oxidative phenotype stimulates cancer-induced muscle wasting. The aim of the current proof of concept study is to validate loss of muscle oxidative phenotype in newly diagnosed patients with lung cancer, especially in those with cachexia. For this, quadriceps muscle biopsies of comprehensively phenotyped pre-cachectic (n=10) and cachectic (n=16) patients with non-small cell lung cancer (NSCLC) prior to treatment were compared with healthy age matched controls (n=22). Muscle oxidative phenotype was determined by assessing muscle fiber type distribution (immunohistochemistry), enzyme activity (spectrophotometry), as well as protein and gene expression levels of mitochondrial components and their regulators. Additionally, muscle fiber cross sectional area (CSA; immunohistochemistry) and systemic inflammation (multiplex analysis) were assessed. We found that muscle fiber CSA was smaller and plasma levels of IL-6 were significantly higher in cachectic patients compared to non-cachectic patients and healthy controls. No differences in muscle fiber 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. Hence we concluded that muscle oxidative phenotype is preserved in newly diagnosed NSCLC and therefore not a primary trigger of cachexia in these patients.