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

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Název: Circulating tryptophan–kynurenine pathway metabolites are associated with all‐cause mortality among patients with stage I–III colorectal cancer
Autoři: Damerell, Victoria, Klaassen‐Dekker, Niels, Brezina, Stefanie, Ose, Jennifer, Ulvik, Arve, Roekel, Eline H. van, Holowatyj, Andreana N., Baierl, Andreas, Böhm, Jürgen, Bours, Martijn J. L., Brenner, Hermann, Wilt, Johannes H. W. de, Grady, William M., Habermann, Nina, Hoffmeister, Michael, Keski‐Rahkonen, Pekka, Lin, Tengda, Schirmacher, Peter, Schrotz‐King, Petra, Ulrich, Alexis B., Duijnhoven, Fränzel J. B. van, Warby, Christy A., Shibata, David, Toriola, Adetunji T., Figueiredo, Jane C., Siegel, Erin M., Li, Christopher I., Gsur, Andrea, Kampman, Ellen, Schneider, Martin, Ueland, Per M., Weijenberg, Matty P., Ulrich, Cornelia M., Kok, Dieuwertje E., Gigic, Biljana
Zdroj: Int J Cancer
International Journal of Cancer, 156, 3, pp. 552-565
Informace o vydavateli: Wiley, 2024.
Rok vydání: 2024
Témata: Male, Xanthurenates, kynurenines, BIOMARKERS, 3-Hydroxyanthranilic Acid, Prognose, colorectal cancer, T-CELL, Kynurenic Acid, Sterblichkeit, RESEARCH ARTICLE, RATIO, INFLAMMATION, QUALITY-OF-LIFE, Biomarkers, Tumor, Dickdarmkrebs, Humans, tryptophan, ortho-Aminobenzoates, ddc:610, Kynurenin, Prospective Studies, Kynurenine, Aged, Neoplasm Staging, RISK, PLASMA, Tryptophan, Middle Aged, Quinolinic Acid, Prognosis, IMMUNE ACTIVATION, 610 Medizin, Gesundheit, CELL PROLIFERATION, all-cause mortality, Female, prognosis, HEALTH, Colorectal Neoplasms, Metabolic Networks and Pathways, Surgery - Radboud University Medical Center
Popis: 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.
Druh dokumentu: Article
Other literature type
Popis souboru: application/pdf
Jazyk: English
ISSN: 1097-0215
0020-7136
DOI: 10.1002/ijc.35183
DOI: 10.25968/opus-3261
Přístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/39308420
https://serwiss.bib.hs-hannover.de/files/3261/damerell_etal2024-tryptophan-kynurenine.pdf
https://repository.ubn.ru.nl//bitstream/handle/2066/313188/313188.pdf
https://hdl.handle.net/2066/313188
Rights: CC BY
Přístupové číslo: edsair.doi.dedup.....3e9f57d71c1e7b61cd112847277b63ee
Databáze: OpenAIRE
Popis
Abstrakt: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.
ISSN:10970215
00207136
DOI:10.1002/ijc.35183