Association of circulating tryptophan-kynurenine pathway metabolites with all-cause mortality in colorectal cancer: pooled analysis of six prospective cohorts

Alterations within the tryptophan-kynurenine pathway have been linked to the etiology of colorectal cancer (CRC), but the prognostic relevance of this pathway for CRC patients needs further elucidation. Analysis of 2102 stage I-III CRC patients in six prospective cohorts of the FOCUS Consortium investigated the association of preoperative concentrations of circulating metabolites of this pathway with all-cause mortality, adjusted for potential confounders. During a median follow-up of 3.2 years (IQR 2.2-4.9), 290 patients (13.8%) deceased. Higher blood concentration of tryptophan (per doubling in concentration HR 0.56; 95% CI 0,41-0,76), xanthurenic acid (0.74; 0.64-0.85), and picolinic acid (0.76; 0.64-0.92) were associated with lower all-cause mortality, whereas higher concentrations of 3-hydroxykurenine (1.80; 1.47-2.21) and quinolinic acid (1.31; 1.05-1.63) were associated with higher all-cause mortality. A higher kynurenine-to-tryptophan ratio, a marker of cell-mediated immune activation, was associated with increased risk of death (per doubling: HR 2.07; 95% CI 1.52-2.83). The authors conclude that tryptophan-kynurenine pathway metabolites may be prognostic markers of survival in CRC patients.