TY - JOUR
T1 - Plasma metabolites associated with colorectal cancer stage: Findings from an international consortium
AU - Geijsen, Anne J.M.R.
AU - van Roekel, Eline H.
AU - van Duijnhoven, Fränzel J.B.
AU - Achaintre, David
AU - Bachleitner-Hofmann, Thomas
AU - Baierl, Andreas
AU - Bergmann, Michael M.
AU - Boehm, Jürgen
AU - Bours, Martijn J.L.
AU - Brenner, Hermann
AU - Breukink, Stéphanie O.
AU - Brezina, Stefanie
AU - Chang-Claude, Jenny
AU - Herpel, Esther
AU - de Wilt, Johannes H.W.
AU - Gicquiau, Audrey
AU - Gigic, Biljana
AU - Gumpenberger, Tanja
AU - Hansson, Bibi M.E.
AU - Hoffmeister, Michael
AU - Holowatyj, Andreana N.
AU - Karner-Hanusch, Judith
AU - Keski-Rahkonen, Pekka
AU - Keulen, Eric T.P.
AU - Koole, Janna L.
AU - Leeb, Gernot
AU - Ose, Jennifer
AU - Schirmacher, Peter
AU - Schneider, Martin A.
AU - Schrotz-King, Petra
AU - Stift, Anton
AU - Ulvik, Arve
AU - Vogelaar, Jeroen F.
AU - Wesselink, Evertine
AU - van Zutphen, Moniek
AU - Gsur, Andrea
AU - Habermann, Nina
AU - Kampman, Ellen
AU - Scalbert, Augustin
AU - Ueland, Per M.
AU - Ulrich, Alexis B.
AU - Ulrich, Cornelia M.
AU - Weijenberg, Matty P.
AU - Kok, Dieuwertje E.
PY - 2020/6/15
Y1 - 2020/6/15
N2 - 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 (pFDR < 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 (pFDR < 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.
AB - 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 (pFDR < 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 (pFDR < 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.
KW - colorectal cancer
KW - disease stage
KW - epidemiology
KW - metabolomics
KW - plasma metabolites
U2 - 10.1002/ijc.32666
DO - 10.1002/ijc.32666
M3 - Article
C2 - 31495913
AN - SCOPUS:85074494276
SN - 0020-7136
VL - 146
SP - 3256
EP - 3266
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 12
ER -
