Metabolomic Profiling of Cancer Cachexia Phenotypes for Targeted Immunonutritional Support in Palliative Patients

Abstract

Cancer cachexia is a multifactorial syndrome that is manifested by intense weight loss, muscle catabolism, and fatigue that profoundly affect the quality of life of patients with advanced cancer. Although it has clinical implications, the metabolic pathophysiology of cachexia is poorly comprehended. The purpose of this study was to investigate the metabolomic profile related to cancer cachexia phenotypes in palliative cancer patients and explore the possibility of immunonutritional support as a therapeutic approach. Clinical criteria were used to categorize plasma samples of 40 patients into either cachexia or non-cachexia. The metabolomic profiling was conducted by liquid chromatography-time-of-flight mass spectrometry (LC-TOF-MS) with the statistical analysis being done with the help of principal component analysis (PCA) and Mann-Whitney U test. Significant differences in metabolite concentrations were observed, with cachexia patients showing lower levels of branched-chain amino acids (valine: 158.3 ± 20.6 µM vs. 210.5 ± 25.2 µM, leucine: 101.2 ± 15.7 µM vs. 138.7 ± 18.4 µM) and tryptophan (33.6 ± 6.4 µM vs. 48.9 ± 5.8 µM), and higher levels of polyamine metabolites (spermidine: 0.158 ± 0.031 µM vs. 0.061 ± 0.012 µM, spermine: 0.131 ± 0.026 µM vs. 0.049 ± 0.010 µM). Following a 4-week targeted immunonutritional intervention, improvements were noted in body weight (53.6 ± 5.1 kg vs. 51.2 ± 5.3 kg, p = 0.006), muscle mass (36.2 ± 3.5% vs. 33.5 ± 3.8%, p = 0.009), and fatigue (FACIT-F score: 37.8 ± 5.2 vs. 30.5 ± 6.3, p = 0.003). The results suggest the promise of metabolomic profiling and individualized immunonutrition in the management of cancer cachexia and fatigue.