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

Author:

das Neves Willian123ORCID,Alves Christiano R. R.234ORCID,dos Santos Gabriela1,Alves Maria‐Janieire N. N.5,Deik Amy6,Pierce Kerry6,Dennis Courtney6,Buckley Lily6,Clish Clary B.6,Swoboda Kathryn J.23,Brum Patricia C.4,de Castro Junior Gilberto1

Affiliation:

1. Faculdade de Medicina, Instituto do Cancer do Estado de Sao Paulo ICESP, Hospital das Clínicas HCFMUSP, Universidade de Sao Paulo Sao Paulo Brazil

2. Center for Genomic Medicine Massachusetts General Hospital Boston Massachusetts USA

3. Department of Neurology Harvard Medical School, Massachusetts General Hospital Boston Massachusetts USA

4. School of Physical Education and Sport University of São Paulo São Paulo Brazil

5. Heart Institute, School of Medicine University of Sao Paulo Sao Paulo Brazil

6. Metabolomics Platform Broad Institute of MIT and Harvard Cambridge Massachusetts USA

Abstract

AbstractBackgroundLow 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.MethodsThis 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.ResultsWe 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.ConclusionThese 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.

Funder

Fundação de Amparo à Pesquisa do Estado de São Paulo

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Publisher

Wiley

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