Circulating tryptophan–kynurenine pathway metabolites are associated with all‐cause mortality among patients with stage I–III colorectal cancer

Alterations within the tryptophan-kynurenine metabolic pathway have been linked to the etiology of colorectal cancer (CRC), but the relevance of this pathway for prognostic outcomes in CRC patients needs further elucidation. Therefore, we investigated associations between circulating concentrations of tryptophan-kynurenine pathway metabolites and all-cause mortality among CRC patients. This study utilizes data from 2102 stage I-III CRC patients participating in six prospective cohorts involved in the international FOCUS Consortium. Preoperative circulating concentrations of tryptophan, kynurenine, kynurenic acid (KA), 3-hydroxykynurenine (HK), xanthurenic acid (XA), 3-hydroxyanthranilic acid (HAA), anthranilic acid (AA), picolinic acid (PA), and quinolinic acid (QA) were measured by liquid chromatography-tandem mass spectrometry. Using Cox proportional hazards regression, we examined associations of above-mentioned metabolites with all-cause mortality, adjusted for potential confounders. During a median follow-up of 3.2 years (interquartile range: 2.2-4.9), 290 patients (13.8%) deceased. Higher blood concentrations of tryptophan, XA, and PA were associated with a lower risk of all-cause mortality (per doubling in concentrations: tryptophan: HR = 0.56; 95%CI:0.41,0.76, XA: HR = 0.74; 95%CI:0.64,0.85, PA: HR = 0.76; 95%CI:0.64,0.92), while higher concentrations of HK and QA were associated with an increased risk of death (per doubling in concentrations: HK: HR = 1.80; 95%CI:1.47,2.21, QA: HR = 1.31; 95%CI:1.05,1.63). A higher kynurenine-to-tryptophan ratio, a marker of cell-mediated immune activation, was associated with an increased risk of death (per doubling: HR = 2.07; 95%CI:1.52,2.83). In conclusion, tryptophan-kynurenine pathway metabolites may be prognostic markers of survival in CRC patients.

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Publication Details

Journal
International Journal of Cancer
Published
2024-09-23
DOI
https://doi.org/10.1002/ijc.35183
Citations
14
Primary Topic
Tryptophan and brain disorders
Type
article
Field-Weighted Citation Impact
2.20

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article

Circulating tryptophan–kynurenine pathway metabolites are associated with all‐cause mortality among patients with stage I–III colorectal cancer

Stefanie Brezina, Ellen Kampman, Dieuwertje E. Kok, Victoria Damerell et al.
14 citations
International Journal of Cancer
Tryptophan and brain disorders
2.20
article

Circulating tryptophan–kynurenine pathway metabolites are associated with all‐cause mortality among patients with stage I–III colorectal cancer

Stefanie Brezina, Ellen Kampman, Dieuwertje E. Kok, Victoria Damerell, Andrea Gsur, Cornelia M. Ulrich, Martijn J.L. Bours, Arve Ulvik, Jane C. Figueiredo, David Shibata, Per Magne Ueland, Matty P. Weijenberg, Michael Hoffmeister, Christopher I. Li, Biljana Gigic, Pekka Keski‐Rahkonen, Erin M. Siegel, Andreana N. Holowatyj, Alexis Ulrich, William M. Grady, Tengda Lin, Christy A. Warby, Andreas Baierl, Jürgen Böhm, Hermann Brenner, Jennifer Ose, Johannes H.W. de Wilt, Eline H. van Roekel, Adetunji T. Toriola, Martin Schneider, Petra Schrotz‐King, Niels Klaassen‐Dekker, Peter Schirmacher, Fränzel J. B. van Duijnhoven
article en
14 citations

Abstract

Alterations within the tryptophan-kynurenine metabolic pathway have been linked to the etiology of colorectal cancer (CRC), but the relevance of this pathway for prognostic outcomes in CRC patients needs further elucidation. Therefore, we investigated associations between circulating concentrations of tryptophan-kynurenine pathway metabolites and all-cause mortality among CRC patients. This study utilizes data from 2102 stage I-III CRC patients participating in six prospective cohorts involved in the international FOCUS Consortium. Preoperative circulating concentrations of tryptophan, kynurenine, kynurenic acid (KA), 3-hydroxykynurenine (HK), xanthurenic acid (XA), 3-hydroxyanthranilic acid (HAA), anthranilic acid (AA), picolinic acid (PA), and quinolinic acid (QA) were measured by liquid chromatography-tandem mass spectrometry. Using Cox proportional hazards regression, we examined associations of above-mentioned metabolites with all-cause mortality, adjusted for potential confounders. During a median follow-up of 3.2 years (interquartile range: 2.2-4.9), 290 patients (13.8%) deceased. Higher blood concentrations of tryptophan, XA, and PA were associated with a lower risk of all-cause mortality (per doubling in concentrations: tryptophan: HR = 0.56; 95%CI:0.41,0.76, XA: HR = 0.74; 95%CI:0.64,0.85, PA: HR = 0.76; 95%CI:0.64,0.92), while higher concentrations of HK and QA were associated with an increased risk of death (per doubling in concentrations: HK: HR = 1.80; 95%CI:1.47,2.21, QA: HR = 1.31; 95%CI:1.05,1.63). A higher kynurenine-to-tryptophan ratio, a marker of cell-mediated immune activation, was associated with an increased risk of death (per doubling: HR = 2.07; 95%CI:1.52,2.83). In conclusion, tryptophan-kynurenine pathway metabolites may be prognostic markers of survival in CRC patients.

International Journal of CancerVol. 156(3)
Cedars-Sinai Medical Center (US), University of Vienna (AT), Hochschule Hannover (DE), Radboud University Nijmegen (NL), University of Tennessee Health Science Center (US), German Cancer Research Center (DE), Washington University in St. Louis (US), University of Utah (US), Heidelberg University (DE), Huntsman Cancer Institute (US), University Hospital Heidelberg (DE), Radboud University Medical Center (NL), Moffitt Cancer Center (US), Maastricht University (NL), Fred Hutch Cancer Center (US), Comprehensive Cancer Center Vienna (AT), National Center for Tumor Diseases (DE), European Molecular Biology Laboratory (DE), Bevital (Norway) (NO), Lukaskrankenhaus (DE), Centre international de recherche sur le cancer (FR), Medical University of Vienna (AT), Vanderbilt University Medical Center (US), Wageningen University & Research (NL)
Fred Hutchinson Cancer Research Center, Kreftforeningen, Huntsman Cancer Foundation, Health Foundation Limburg, Universiteit Maastricht, Bundesministerium für Bildung und Forschung, Austrian Science Fund, Maastricht Universitair Medisch Centrum, Wereld Kanker Onderzoek Fonds, Heidelberger Stiftung Chirurgie, National Institutes of Health, Wageningen University and Research, National Cancer Institute
Good health and well-being
Openalex Percentile: Top 11%
Tryptophan and brain disorders
2.20
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