Dataset Information

Multiplatform Urinary Metabolomics Profiling to Discriminate Cachectic from Non-Cachectic Colorectal Cancer Patients: Pilot Results from the ColoCare Study.

ABSTRACT: Cachexia is a multifactorial syndrome that is characterized by loss of skeletal muscle mass in cancer patients. The biological pathways involved remain poorly characterized. Here, we compare urinary metabolic profiles in newly diagnosed colorectal cancer patients (stage I-IV) from the ColoCare Study in Heidelberg, Germany. Patients were classified as cachectic (n = 16), pre-cachectic (n = 13), or non-cachectic (n = 23) based on standard criteria on weight loss over time at two time points. Urine samples were collected pre-surgery, and 6 and 12 months thereafter. Fat and muscle mass area were assessed utilizing computed tomography scans at the time of surgery. N = 152 compounds were detected using untargeted metabolomics with gas chromatography-mass spectrometry and n = 154 features with proton nuclear magnetic resonance spectroscopy. Thirty-four metabolites were overlapping across platforms. We calculated differences across groups and performed discriminant and overrepresentation enrichment analysis. We observed a trend for 32 compounds that were nominally significantly different across groups, although not statistically significant after adjustment for multiple testing. Nineteen compounds could be identified, including acetone, hydroquinone, and glycine. Comparing cachectic to non-cachectic patients, higher levels of metabolites such as acetone (Fold change (FC) = 3.17; p = 0.02) and arginine (FC = 0.33; p = 0.04) were observed. The two top pathways identified were glycerol phosphate shuttle metabolism and glycine and serine metabolism pathways. Larger subsequent studies are needed to replicate and validate these results.

SUBMITTER: Ose J

PROVIDER: S-EPMC6780796 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Multiplatform Urinary Metabolomics Profiling to Discriminate Cachectic from Non-Cachectic Colorectal Cancer Patients: Pilot Results from the ColoCare Study.

Ose Jennifer J Gigic Biljana B Lin Tengda T Liesenfeld David B DB Böhm Jürgen J Nattenmüller Johanna J Scherer Dominique D Zielske Lin L Schrotz-King Petra P Habermann Nina N Ochs-Balcom Heather M HM Peoples Anita R AR Hardikar Sheetal S Li Christopher I CI Shibata David D Figueiredo Jane J Toriola Adetunji T AT Siegel Erin M EM Schmit Stephanie S Schneider Martin M Ulrich Alexis A Kauczor Hans-Ulrich HU Ulrich Cornelia M CM

Metabolites 20190906 9

Cachexia is a multifactorial syndrome that is characterized by loss of skeletal muscle mass in cancer patients. The biological pathways involved remain poorly characterized. Here, we compare urinary metabolic profiles in newly diagnosed colorectal cancer patients (stage I-IV) from the ColoCare Study in Heidelberg, Germany. Patients were classified as cachectic (n = 16), pre-cachectic (n = 13), or non-cachectic (n = 23) based on standard criteria on weight loss over time at t ...[more]

PMID: 31500101

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Project description:BackgroundMetabolic and transcriptomic differences between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) compartments, particularly in the context of obesity, may play a role in colorectal carcinogenesis. We investigated the differential functions of their metabolic compositions.ObjectivesBiochemical differences between adipose tissues (VAT compared with SAT) in patients with colorectal carcinoma (CRC) were investigated by using mass spectrometry metabolomics and gene expression profiling. Metabolite compositions were compared between VAT, SAT, and serum metabolites. The relation between patients' tumor stage and metabolic profiles was assessed.DesignPresurgery blood and paired VAT and SAT samples during tumor surgery were obtained from 59 CRC patients (tumor stages I-IV) of the ColoCare cohort. Gas chromatography time-of-flight mass spectrometry and liquid chromatography quadrupole time-of-flight mass spectrometry were used to measure 1065 metabolites in adipose tissue (333 identified compounds) and 1810 metabolites in serum (467 identified compounds). Adipose tissue gene expression was measured by using Illumina's HumanHT-12 Expression BeadChips.ResultsCompared with SAT, VAT displayed elevated markers of inflammatory lipid metabolism, free arachidonic acid, phospholipases (PLA2G10), and prostaglandin synthesis-related enzymes (PTGD/PTGS2S). Plasmalogen concentrations were lower in VAT than in SAT, which was supported by lower gene expression of FAR1, the rate-limiting enzyme for ether-lipid synthesis in VAT. Serum sphingomyelin concentrations were inversely correlated (P = 0.0001) with SAT adipose triglycerides. Logistic regression identified lipids in patients' adipose tissues, which were associated with CRC tumor stage.ConclusionsAs one of the first studies, we comprehensively assessed differences in metabolic, lipidomic, and transcriptomic profiles between paired human VAT and SAT and their association with CRC tumor stage. We identified markers of inflammation in VAT, which supports prior evidence regarding the role of visceral adiposity and cancer.

Dataset Information

Multiplatform Urinary Metabolomics Profiling to Discriminate Cachectic from Non-Cachectic Colorectal Cancer Patients: Pilot Results from the ColoCare Study.

Publications

Multiplatform Urinary Metabolomics Profiling to Discriminate Cachectic from Non-Cachectic Colorectal Cancer Patients: Pilot Results from the ColoCare Study.

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