Journal Article

DKFZ-2024-01910

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Circulating tryptophan-kynurenine pathway metabolites are associated with all-cause mortality among patients with stage I-III colorectal cancer.

Damerell, V. ; Klaassen-Dekker, N. ; Brezina, S. ; Ose, J. ; Ulvik, A. ; van Roekel, E. H. ; Holowatyj, A. N. ; Baierl, A. ; Böhm, J. ; Bours, M. J. L. ; Brenner, H.DKFZ* ; de Wilt, J. H. W. ; Grady, W. M. ; Habermann, N. ; Hoffmeister, M.DKFZ* ; Keski-Rahkonen, P. ; Lin, T. ; Schirmacher, P. ; Schrotz-King, P.DKFZ* ; Ulrich, A. B. ; van Duijnhoven, F. J. B. ; Warby, C. A. ; Shibata, D. ; Toriola, A. T. ; Figueiredo, J. C. ; Siegel, E. M. ; Li, C. I. ; Gsur, A. ; Kampman, E. ; Schneider, M. ; Ueland, P. M. ; Weijenberg, M. P. ; Ulrich, C. M. ; Kok, D. E. ; Gigic, B. ; Consortium, F. (Collaboration Author)

2025
Wiley-Liss Bognor Regis

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Please use a persistent id in citations: doi:10.1002/ijc.35183

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.

Keyword(s): all‐cause mortality ; colorectal cancer ; kynurenines ; prognosis ; tryptophan

Note: 2025 Feb 1;156(3):552-565

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Contributing Institute(s):

1. C070 Klinische Epidemiologie und Alternf. (C070)
2. Präventive Onkologie (C120)
3. DKTK HD zentral (HD01)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2024

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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