Associations of branched-chain amino acids with parameters of energy balance and survival in colorectal cancer patients: Results from the ColoCare Study.

Abstract

Branched-chain amino acids (BCAA) have been previously linked to survival in colorectal cancer (CRC) patients. It is unclear whether BCAAs are prognostic biomarkers or surrogate markers for energy balance. We aimed to determine correlations of BCAAs with markers of energy balance over time and to investigate prognostic significance of BCAAs in CRC. We used urinary samples from newly diagnosed CRC patients [n=163; (stage I - IV)] from the ColoCare study in Heidelberg, Germany, collected at surgery (n=163), 6 (n=83) and 12 months follow-up (n=54). Isoleucine, leucine, valine, (2Z)-3-methylglutaconic acid (3HM), 2-ethylhydracrylic acid (2EA), 2-methyl-3-hydroxybutyrate (2M3H) were detected using gas-chromatography mass-spectrometry and proton-nuclear-magnetic-resonance spectroscopy. Partial correlation coefficients between BCAAs with body mass index (BMI), physical activity (metabolic equivalent [MET]) and muscle area were computed and adjusted for sex and age at diagnosis. We used Cox proportional hazard models to investigate overall survival (OS) after 24 months of follow-up. We did not observe significant correlations between BCAAs and parameters of energy balance at all time points (correlation ranges: BMI: r= -0.13 to -0.01; METs: r=-0.14 to 0.02; dorsal muscle: r=-0.03 to 0.10). BCAAs were not associated with risk of death in stage I-III (e.g., valine: HRlog2=1.62, p=0.25) or in stage IV tumors. Elevated concentrations of 2EA and 2M3H were significantly associated with OS, independent of stage (2EA: stage I-III: HRlog2=0.42, p=0.04; stage IV: HRlog2=0.51, p=0.01). Our study suggests that BCAAs in colorectal cancer patients do not reflect parameters of energy balance and may be independently associated with overall survival.