Physical performance and plasma metabolic profile as potential prognostic factors in metastatic lung cancer patients.

Background: Low physical performance is associated with higher mortality rate in multiple pathological conditions. Here, we aimed to determine whether body composition and physical performance could be prognostic factors in non‐small cell lung cancer (NSCLC) patients. Moreover, we performed an exploratory approach to determine whether plasma samples from NSCLC patients could directly affect metabolic and structural phenotypes in primary muscle cells. Methods: This prospective cohort study included 55 metastatic NSCLC patients and seven age‐matched control subjects. Assessments included physical performance, body composition, quality of life and overall survival rate. Plasma samples from a sub cohort of 18 patients were collected for exploratory studies in cell culture and metabolomic analysis. Results: We observed a higher survival rate in NSCLC patients with high performance in the timed up‐and‐go (+320%; p =.007), sit‐to‐stand (+256%; p =.01) and six‐minute walking (+323%; p =.002) tests when compared to NSCLC patients with low physical performance. There was no significant association for similar analysis with body composition measurements (p >.05). Primary human myotubes incubated with plasma from NSCLC patients with low physical performance had impaired oxygen consumption rate (−54.2%; p <.0001) and cell proliferation (−44.9%; p =.007). An unbiased metabolomic analysis revealed a list of specific metabolites differentially expressed in the plasma of NSCLC patients with low physical performance. Conclusion: These novel findings indicate that physical performance is a prognostic factor for overall survival in NSCLC patients and provide novel insights into circulating factors that could impair skeletal muscle metabolism. We found that patients with better performance in the timed up‐and‐go, sit‐to‐stand and six‐minutes walking test lived longer in this cohort. Moreover, plasma from NSCLC patients with low physical performance impaired oxygen consumption and extracellular acidification rate and decreased the proliferation of primary human myotubes. Unbiased metabolomics revealed several metabolites differentially expressed in the plasma of NSCLC patients with low physical performance compared to healthy control subjects, with serine and M22G being the most reduced and increased metabolites, respectively. [ABSTRACT FROM AUTHOR]