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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...

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Main Authors: Damerell, Victoria (Author) , Klaassen-Dekker, Niels (Author) , Brezina, Stefanie (Author) , Ose, Jennifer (Author) , Ulvik, Arve (Author) , van Roekel, Eline H. (Author) , Holowatyj, Andreana N. (Author) , Baierl, Andreas (Author) , Böhm, Jürgen (Author) , Bours, Martijn J. L. (Author) , Brenner, Hermann (Author) , de Wilt, Johannes H. W. (Author) , Grady, William M. (Author) , Habermann, Nina (Author) , Hoffmeister, Michael (Author) , Keski-Rahkonen, Pekka (Author) , Lin, Tengda (Author) , Schirmacher, Peter (Author) , Schrotz-King, Petra (Author) , Ulrich, Alexis B. (Author) , van Duijnhoven, Fränzel J. B. (Author) , Warby, Christy A. (Author) , Shibata, David (Author) , Toriola, Adetunji T. (Author) , Figueiredo, Jane C. (Author) , Siegel, Erin M. (Author) , Li, Christopher I. (Author) , Gsur, Andrea (Author) , Kampman, Ellen (Author) , Schneider, Martin (Author) , Ueland, Per M. (Author) , Weijenberg, Matty P. (Author) , Ulrich, Cornelia M. (Author) , Kok, Dieuwertje E. (Author) , Gigić, Biljana (Author)
Format: Article (Journal)
Language:English
Published: [23 September 2024]
In: International journal of cancer
Year: 2025, Volume: 156, Issue: 3, Pages: 552-565
ISSN:1097-0215
DOI:10.1002/ijc.35183
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1002/ijc.35183
Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.35183
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Author Notes:Victoria Damerell, Niels Klaassen-Dekker, Stefanie Brezina, Jennifer Ose, Arve Ulvik, Eline H. van Roekel, Andreana N. Holowatyj, Andreas Baierl, Jürgen Böhm, Martijn J. L. Bours, Hermann Brenner, Johannes H. W. de Wilt, William M. Grady, Nina Habermann, Michael Hoffmeister, Pekka Keski-Rahkonen, Tengda Lin, Peter Schirmacher, Petra Schrotz-King, Alexis B. Ulrich, Fränzel J. B. van Duijnhoven, Christy A. Warby, David Shibata, Adetunji T. Toriola, Jane C. Figueiredo, Erin M. Siegel, Christopher I. Li, Andrea Gsur, Ellen Kampman, Martin Schneider, Per M. Ueland, Matty P. Weijenberg, Cornelia M. Ulrich, Dieuwertje E. Kok, Biljana Gigic, Focus Consortium
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Summary: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.
Item Description:Gesehen am 23.05.2025
Physical Description:Online Resource
ISSN:1097-0215
DOI:10.1002/ijc.35183

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