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Higher Plasma Creatinine Is Associated with an Increased Risk of Death in Patients with Non-Metastatic Rectal but Not Colon Cancer: Results from an International Cohort Consortium

  • Colorectal cancer (CRC) is increasingly recognized as a heterogeneous disease. No studies have prospectively examined associations of blood metabolite concentrations with all-cause mortality in patients with colon and rectal cancer separately. Targeted metabolomics (Biocrates AbsoluteIDQ p180) and pathway analyses (MetaboAnalyst 4.0) were performed on pre-surgery collected plasma from 674 patients with non-metastasized (stage I–III) colon (n = 394) or rectal cancer (n = 283). Metabolomics data and covariate information were received from the international cohort consortium MetaboCCC. Cox proportional hazards models were computed to investigate associations of 148 metabolite levels with all-cause mortality adjusted for age, sex, tumor stage, tumor site (whenever applicable), and cohort; the false discovery rate (FDR) was used to account for multiple testing. A total of 93 patients (14%) were deceased after an average follow-up time of 4.4 years (60 patients with colon cancer and 33 patients with rectal cancer). After FDR adjustment, higher plasma creatinine was associated with a 39% increase in all-cause mortality in patients with rectal cancer. HR: 1.39, 95% CI 1.23–1.72, pFDR = 0.03; but not colon cancer: pFDR = 0.96. Creatinine is a breakdown product of creatine phosphate in muscle and may reflect changes in skeletal muscle mass. The starch and sucrose metabolisms were associated with increased all-cause mortality in colon cancer but not in rectal cancer. Genes in the starch and sucrose metabolism pathways were previously linked to worse clinical outcomes in CRC. In summary, our findings support the hypothesis that colon and rectal cancer have different etiological and clinical outcomes that need to be considered for targeted treatments.

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Author:Jennifer OseORCiDGND, Biljana GigicORCiD, Stefanie Brezina, Tengda Lin, Anita R. Peoples, Pauline P. SchobertORCiD, Andreas BaierlORCiD, Eline van RoekelORCiD, Nivonirina RobinotORCiD, Audrey Gicquiau, David Achaintre, Augustin ScalbertORCiD, Fränzel J. B. van Duijnhoven, Andreana N. HolowatyjORCiD, Tanja GumpenbergerORCiD, Petra Schrotz-KingORCiD, Alexis B. Ulrich, Arve Ulvik, Per-Magne Ueland, Matty P. Weijenberg, Nina Habermann, Pekka Keski-RahkonenORCiD, Andrea GsurORCiD, Dieuwertje E. KokORCiD, Cornelia M. UlrichORCiD
DOI original:https://doi.org/10.3390/cancers15133391
Parent Title (English):Cancers
Document Type:Article
Year of Completion:2023
Publishing Institution:Hochschule Hannover
Release Date:2024/05/07
Tag:all-cause mortality; colon cancer; creatinine; metabolites; rectal cancer; starch and sucrose pathway
GND Keyword:Sterblichkeit; Kreatinin; Metabolit; Darmkrebs; Mastdarmkrebs
Article Number:3391
Page Number:15
Institutes:Fakultät III - Medien, Information und Design
DDC classes:610 Medizin, Gesundheit
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International