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
Year: 2023
Type: article
Study design: Observational Study
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.
Source: Cancers
Authors: 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. Weijenberg, Nina Habermann, Pekka Keski-Rahkonen, Andrea Gsur, Dieuwertje E. Kok, Cornelia M. Ulrich
Institutions: University of Utah, Huntsman Cancer Institute, Heidelberg University, Medical University of Vienna, Technical University of Munich, Ludwig-Maximilians-Universität München, University of Vienna, Maastricht University, Centre international de recherche sur le cancer, Wageningen University & Research, Vanderbilt University, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, German Cancer Research Center, National Center for Tumor Diseases, Bevital (Norway), European Molecular Biology Laboratory
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,892
Funders: World Health Organization, Huntsman Cancer Foundation, Universiteit Maastricht, Bundesministerium für Bildung und Forschung, Universität Wien, Maastricht Universitair Medisch Centrum, KWF Kankerbestrijding, Norges Forskningsråd, Medizinische Universität Wien, Institut National Du Cancer, Wereld Kanker Onderzoek Fonds, National Institutes of Health, Wageningen University and Research, National Human Genome Research Institute, National Cancer Institute, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1186363347, Discovery and verification of novel biomarkers of colorectal cancer recurrence, G1306141025, G1394154822, G1693460249, G1700456199, G1703766442, G1783890911, PerMiCCion - Ein personalisierter mikrobiom-basierter Ansatz zur Prävention, Diagnose und Behandlung von früh-einsetzendem Darmkrebs - Standort Heidelberg, G1897774367, Global metabolomics profiling, dietary factors, and colorectal cancer risk in the NIH-Consortium of Metabolomics Studies (COMETS), G192815613, G1945543362, G1993013524, G2020740227, G2026003582, G2133306515, G2143506349, G214363526, G2277753665, G2422275485, G2660915896, G2735014354, G2738098239, G278715299, G2801751686, G2874260318, G2900769747, TRANSCAN III - Verbund: Biomarker des Folatstoffwechsels und deren Assoziation mit der Prognose des kolorektalen Karzinoms, G3281335288, G3439432689, G3528710057, G35565251, G3561730875, G3772360457, G388930096, G3906874468, G3911183554, G3938599196, G3938901433, G3947642476, G3995233724, G4234380927, G4290755586, G4321505744, G4378922882, G4578691124, G4636665230, G4864901413, Metabolomic Strategies for Discovery and Validation of Biomarkers of Colorectal Cancer Recurrence, G5101756463, G5163121640, G5343337284, G5436063499, G5447567428, G5633632810, G5685249982, G5894189799, G5939395570, G5954088288, G6042843351, G6058434148, TRANSCAN II - Verbund: Das metabolomische Profil im Kontinuum der kolorektalen Karzinogenese (TP 1, 3, 4), G6129745028, G6220497479, G6343507173, G6462325963, G6505421423, G6734998282, Building Interdisciplinary Research Careers in Women's Health, G7000839933, G706769298, G7311914060, G7383679059, G7474122295, G7565346878, G7593874140, G7629010839, G779949835, G7829886713, G8289068480, G836149003, G8597501631, G8688917160, G8720654482, G8802764557, G8816854169, G8817804706, G8912345456, G8945434441, Training Program in Genomic Medicine, Building Interdisciplinary Research Careers in Women's Health, Transdisciplinary Team Science in Colorectal Cancer Prognosis: the ColoCare Study
OpenAlex ID: W4382724478