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Plasma metabolites associated with colorectal cancer stage: Findings from an international consortium
Author(s) -
Geijsen Anne J.M.R.,
Roekel Eline H.,
Duijnhoven Fränzel J.B.,
Achaintre David,
BachleitnerHofmann Thomas,
Baierl Andreas,
Bergmann Michael M.,
Boehm Jürgen,
Bours Martijn J.L.,
Brenner Hermann,
Breukink Stéphanie O.,
Brezina Stefanie,
ChangClaude Jenny,
Herpel Esther,
Wilt Johannes H.W.,
Gicquiau Audrey,
Gigic Biljana,
Gumpenberger Tanja,
Hansson Bibi M.E.,
Hoffmeister Michael,
Holowatyj Andrea.,
KarnerHanusch Judith,
KeskiRahkonen Pekka,
Keulen Eric T.P.,
Koole Janna L.,
Leeb Gernot,
Ose Jennifer,
Schirmacher Peter,
Schneider Martin A.,
SchrotzKing Petra,
Stift Anton,
Ulvik Arve,
Vogelaar F. Jeroen,
Wesselink Evertine,
Zutphen Moniek,
Gsur Andrea,
Habermann Nina,
Kampman Ellen,
Scalbert Augustin,
Ueland Per M.,
Ulrich Alexis B.,
Ulrich Cornelia M.,
Weijenberg Matty P.,
Kok Dieuwertje E.
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32666
Subject(s) - colorectal cancer , medicine , cancer , metabolite , sphingomyelin , gastroenterology , oncology , stage (stratigraphy) , endocrinology , biology , cholesterol , paleontology
Colorectal cancer is the second most common cause of cancer‐related death globally, with marked differences in prognosis by disease stage at diagnosis. We studied circulating metabolites in relation to disease stage to improve the understanding of metabolic pathways related to colorectal cancer progression. We investigated plasma concentrations of 130 metabolites among 744 Stages I–IV colorectal cancer patients from ongoing cohort studies. Plasma samples, collected at diagnosis, were analyzed with liquid chromatography‐mass spectrometry using the Biocrates AbsoluteIDQ™ p180 kit. We assessed associations between metabolite concentrations and stage using multinomial and multivariable logistic regression models. Analyses were adjusted for potential confounders as well as multiple testing using false discovery rate (FDR) correction. Patients presented with 23, 28, 39 and 10% of Stages I–IV disease, respectively. Concentrations of sphingomyelin C26:0 were lower in Stage III patients compared to Stage I patients ( p FDR < 0.05). Concentrations of sphingomyelin C18:0 and phosphatidylcholine (diacyl) C32:0 were statistically significantly higher, while citrulline, histidine, phosphatidylcholine (diacyl) C34:4, phosphatidylcholine (acyl‐alkyl) C40:1 and lysophosphatidylcholines (acyl) C16:0 and C17:0 concentrations were lower in Stage IV compared to Stage I patients ( p FDR < 0.05). Our results suggest that metabolic pathways involving among others citrulline and histidine, implicated previously in colorectal cancer development, may also be linked to colorectal cancer progression.