Longitudinal associations of plasma metabolites with persistent fatigue among colorectal cancer survivors up to 2 years after treatment
© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC..
The underlying biological mechanisms causing persistent fatigue complaints after colorectal cancer treatment need further investigation. We investigated longitudinal associations of circulating concentrations of 138 metabolites with total fatigue and subdomains of fatigue between 6 weeks and 2 years after colorectal cancer treatment. Among stage I-III colorectal cancer survivors (n = 252), blood samples were obtained at 6 weeks, and 6, 12 and 24 months posttreatment. Total fatigue and fatigue subdomains were measured using a validated questionnaire. Tandem mass spectrometry was applied to measure metabolite concentrations (BIOCRATES AbsoluteIDQp180 kit). Confounder-adjusted longitudinal associations were analyzed using linear mixed models, with false discovery rate (FDR) correction. We assessed interindividual (between-participant differences) and intraindividual longitudinal associations (within-participant changes over time). In the overall longitudinal analysis, statistically significant associations were observed for 12, 32, 17 and three metabolites with total fatigue and the subscales "fatigue severity," "reduced motivation" and "reduced activity," respectively. Specifically, higher concentrations of several amino acids, lysophosphatidylcholines, diacylphosphatidylcholines, acyl-alkylphosphatidylcholines and sphingomyelins were associated with less fatigue, while higher concentrations of acylcarnitines were associated with more fatigue. For "fatigue severity," associations appeared mainly driven by intraindividual associations, while for "reduced motivation" stronger interindividual associations were found. We observed longitudinal associations of several metabolites with total fatigue and fatigue subscales, and that intraindividual changes in metabolites over time were associated with fatigue severity. These findings point toward inflammation and an impaired energy metabolism due to mitochondrial dysfunction as underlying mechanisms. Mechanistic studies are necessary to determine whether these metabolites could be targets for intervention.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2023 |
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Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:152 |
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Enthalten in: |
International journal of cancer - 152(2023), 2 vom: 15. Jan., Seite 214-226 |
Sprache: |
Englisch |
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Beteiligte Personen: |
van Roekel, Eline H [VerfasserIn] |
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Links: |
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Themen: |
Amino acids |
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Anmerkungen: |
Date Completed 22.11.2022 Date Revised 24.03.2024 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1002/ijc.34252 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM345720067 |
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245 | 1 | 0 | |a Longitudinal associations of plasma metabolites with persistent fatigue among colorectal cancer survivors up to 2 years after treatment |
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520 | |a The underlying biological mechanisms causing persistent fatigue complaints after colorectal cancer treatment need further investigation. We investigated longitudinal associations of circulating concentrations of 138 metabolites with total fatigue and subdomains of fatigue between 6 weeks and 2 years after colorectal cancer treatment. Among stage I-III colorectal cancer survivors (n = 252), blood samples were obtained at 6 weeks, and 6, 12 and 24 months posttreatment. Total fatigue and fatigue subdomains were measured using a validated questionnaire. Tandem mass spectrometry was applied to measure metabolite concentrations (BIOCRATES AbsoluteIDQp180 kit). Confounder-adjusted longitudinal associations were analyzed using linear mixed models, with false discovery rate (FDR) correction. We assessed interindividual (between-participant differences) and intraindividual longitudinal associations (within-participant changes over time). In the overall longitudinal analysis, statistically significant associations were observed for 12, 32, 17 and three metabolites with total fatigue and the subscales "fatigue severity," "reduced motivation" and "reduced activity," respectively. Specifically, higher concentrations of several amino acids, lysophosphatidylcholines, diacylphosphatidylcholines, acyl-alkylphosphatidylcholines and sphingomyelins were associated with less fatigue, while higher concentrations of acylcarnitines were associated with more fatigue. For "fatigue severity," associations appeared mainly driven by intraindividual associations, while for "reduced motivation" stronger interindividual associations were found. We observed longitudinal associations of several metabolites with total fatigue and fatigue subscales, and that intraindividual changes in metabolites over time were associated with fatigue severity. These findings point toward inflammation and an impaired energy metabolism due to mitochondrial dysfunction as underlying mechanisms. Mechanistic studies are necessary to determine whether these metabolites could be targets for intervention | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a amino acids | |
650 | 4 | |a cancer-related fatigue | |
650 | 4 | |a colorectal cancer | |
650 | 4 | |a phospholipids | |
650 | 4 | |a targeted metabolomics | |
700 | 1 | |a Bours, Martijn J L |e verfasserin |4 aut | |
700 | 1 | |a Breukink, Stéphanie O |e verfasserin |4 aut | |
700 | 1 | |a Aquarius, Michèl |e verfasserin |4 aut | |
700 | 1 | |a Keulen, Eric T P |e verfasserin |4 aut | |
700 | 1 | |a Gicquiau, Audrey |e verfasserin |4 aut | |
700 | 1 | |a Rinaldi, Sabina |e verfasserin |4 aut | |
700 | 1 | |a Vineis, Paolo |e verfasserin |4 aut | |
700 | 1 | |a Arts, Ilja C W |e verfasserin |4 aut | |
700 | 1 | |a Gunter, Marc J |e verfasserin |4 aut | |
700 | 1 | |a Leitzmann, Michael F |e verfasserin |4 aut | |
700 | 1 | |a Scalbert, Augustin |e verfasserin |4 aut | |
700 | 1 | |a Weijenberg, Matty P |e verfasserin |4 aut | |
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