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

Jennifer Ose*, Biljana Gigic, Stefanie Brezina, Tengda Lin, Anita R. Peoples, Pauline P. Schobert, Andreas Baierl, Eline van Roekel, Nivonirina Robinot, Audrey Gicquiau, David Achaintre, Augustin Scalbert, Fränzel J.B. van Duijnhoven, Andreana N. Holowatyj, Tanja Gumpenberger, Petra Schrotz-King, Alexis B. Ulrich, Arve Ulvik, Per Magne Ueland, Matty P. WeijenbergNina Habermann, Pekka Keski-Rahkonen, Andrea Gsur, Dieuwertje E. Kok, Cornelia M. Ulrich

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Article number3391
JournalCancers
Volume15
Issue number13
DOIs
Publication statusPublished - Jul 2023

Keywords

  • all-cause mortality
  • colon cancer
  • creatinine
  • metabolites
  • rectal cancer
  • starch and sucrose pathway

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