Targeted plasma metabolic profiles and risk of recurrence in stage ii and iii colorectal cancer patients: Results from an international cohort consortium

Jennifer Ose, Biljana Gigic, Stefanie Brezina, Tengda Lin, Andreas Baierl, Anne J. M. R. Geijsen, Eline van Roekel, Nivonirina Robinot, Audrey Gicquiau, David Achaintre, Pekka Keski‐rahkonen, Fränzel J. B. van Duijnhoven, Tanja Gumpenberger, Andreana N. Holowatyj, Dieuwertje E. Kok, Annaleen Koole, Petra Schrotz‐king, Alexis B. Ulrich, Martin Schneider, Arve UlvikPer-Magne Ueland, Matty P. Weijenberg, Nina Habermann, Augustin Scalbert, Andrea Gsur, Cornelia M. Ulrich

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

The identification of patients at high‐risk for colorectal cancer (CRC) recurrence remains an unmet clinical need. The aim of this study was to investigate associations of metabolites with risk of recurrence in stage II/III CRC patients. A targeted metabolomics assay (128 metabolites measured) was performed on pre‐surgery collected EDTA plasma samples from n = 440 newly diagnosed stage II/III CRC patients. Patients have been recruited from four prospective cohort studies as part of an international consortium: Metabolomic profiles throughout the continuum of CRC (MetaboCCC). Cox proportional hazard models were computed to investigate associations of metabolites with recurrence, adjusted for age, sex, tumor stage, tumor site, body mass index, and cohort; false discovery rate (FDR) was used to account for multiple testing. Sixty‐nine patients (15%) had a recurrence after a median follow‐up time of 20 months. We identified 13 metabolites that were nominally associated with a reduced risk of recurrence. None of the associations were statistically significant after controlling for multiple testing. Pathway topology analyses did not reveal statistically significant associations between recurrence and alterations in metabolic pathways (e.g., sphingolipid metabolism p = 0.04; pFDR = 1.00). To conclude, we did not observe statistically significant associations between metabolites and CRC recurrence using a well‐established metabolomics assay. The observed results require follow‐up in larger studies.
Original languageEnglish
Article number129
Pages (from-to)1-16
JournalMetabolites
Volume11
Issue number3
DOIs
Publication statusPublished - 1 Mar 2021
Externally publishedYes

Funding

Funding: The COLON study was supported by Wereld Kanker Onderzoek Fonds (WKOF) & World Cancer Research Fund International (WCRF International); the World Cancer Research Fund International Regular Grant Programme (WKOF/WCRF, the Netherlands, project no. 2014/1179); Alpe d’Huzes/Dutch Cancer Society (KWF Kankerbestrijding, the Netherlands, project no. UM 2012‐5653, UW 2013‐5927, UW 2015‐7946); ERA‐NET on Translational Cancer Research (TRANSCAN/Dutch Cancer Society, the Netherlands, project no. UW 2013‐6397, UW 2014‐6877); the Netherlands Organization for Health Research and Development (ZonMw, the Netherlands). The EnCoRe study was supported by grants from the Stichting Alpe d’HuZes within the research program ‘Leven met kanker’ of the Dutch Cancer Society (Grant No. UM‐2010‐4867 and UM‐2012‐ 5653), grants from Kankeronderzoekfonds Limburg as part of Health Foundation Limburg (Grant No. 00005739), Wereld Kanker Onderzoek Fonds (WKOF), as part of the World Cancer Research Fund International grant programme (grant number 2016/1620), and ERA‐NET on Translational Cancer Research (TRANSCAN/Dutch Cancer Society, the Netherlands, project no. UM 2014‐6877). E.H. van Roekel is funded by the Wereld Kanker Onderzoek Fonds (WKOF), as part of the World Cancer Research Fund International grant programme (grant number 2016/1620). ColoCare Heidelberg was funded by the ERA‐NET on Translational Cancer Research (TRANSCAN) project 01KT1503 (Federal Ministry of Education and Research), the National Cancer Institute project R01 CA189184, the Stiftung Lebensblicke, and Matthias Lackas Foundation. Investigators at Huntsman Cancer Institute were supported by grants from the National Institutes of Health/NationalCancer Institute (U01CA206110, R01CA189184 and R01 CA207371 to C. M. Ulrich), the Stiftung LebensBlicke, and the Huntsman Cancer Foundation. CORSA was funded by the Austrian Science Fund (FWF), grant no: 1578‐B19. Metabolomics analyses at IARC were funded by the National Cancer Institute (France, project no. 2014‐007). A.N.H. was supported by the National Institutes of Health under Ruth L. Kirschstein National Research Service Award T32 HG008962 from the National Human Genome Research Institute.

FundersFunder number
ERA‐NET on Translational Cancer Research
NationalCancer Institute
Stichting Alpe d’HuZesUM 2012‐5653, 00005739, UM‐2010‐4867
Stiftung LebensBlicke
TRANSCANUW 2013‐6397, UW 2014‐6877
National Institutes of HealthR01 CA207371, U01CA206110
National Human Genome Research Institute
National Cancer InstituteR01 CA189184
Huntsman Cancer Foundation
World Cancer Research Fund International2016/1620, UM 2014‐6877, 01KT1503
Matthias Lackas-Stiftung
World Cancer Research Fund2014/1179
ZonMw
Bundesministerium für Bildung und Forschung
Austrian Science Fund1578‐B19, 2014‐007, T32 HG008962
KWF KankerbestrijdingUW 2013‐5927, UW 2015‐7946
Wereld Kanker Onderzoek Fonds

    Fingerprint

    Dive into the research topics of 'Targeted plasma metabolic profiles and risk of recurrence in stage ii and iii colorectal cancer patients: Results from an international cohort consortium'. Together they form a unique fingerprint.

    Cite this