NMR‐based metabolomics of biofluids in cancer

Giskeødegård, Guro F.; Madssen, Torfinn Støve; Euceda, Leslie R.; Tessem, May‐Britt; Moestue, Siver Andreas; Bathen, Tone Frost

doi:10.1002/nbm.3927

Cited by 35 publications

(26 citation statements)

References 120 publications

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“…Despite the fact that systemic metabolite concentrations are functional read outs of the numerous homeostatic reactions in the body, which will blur the contribution from the cancer cell metabolism to the serum levels [18], our present observation of positive correlation between larger tumor size and increasing S-lactate is supported by Hui S et al [30]. Thus, this indicates that tumor cells may have a substantial contribution to the systemic lactate and pyruvate levels.…”

Section: Discussionsupporting

confidence: 64%

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Metabolic consequences of perioperative oral carbohydrates in breast cancer patients: An explorative study

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Austdal

Bathen

et al. 2019

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Background: The metabolic consequences of preoperative carbohydrate load in breast cancer patients are not known. The present study investigated the systemic and tumor metabolic changes after preoperative per-oral carbohydrate load and their influence on tumor characteristics and survival. Design: Explorative study. Setting: University hospital with primary and secondary care functions in south-west Norway.Interventions and Outcome Measures: Serum and tumor tissue were sampled from a population-based cohort of 60 patients with operable breast cancer who were randomized to either per-oral carbohydrate load (preOp™; n=25) or standard pre-operative fasting (n=35) before surgery. Magnetic resonance (MR) metabolomics was performed on serum samples from all patients and high-resolution magic angle spinning (HR-MAS) MR analysis on 13 tumor samples available from the fasting group and 16 tumor samples from the carbohydrate group. Results: Fourteen of 28 metabolites were differently expressed between fasting and carbohydrate groups. Partial least squares discriminant analysis showed a significant difference in the metabolic profile between the fasting and carbohydrate groups, compatible with the endocrine effects of insulin (i.e., increased serum-lactate and pyruvate and decreased ketone bodies and amino acids in the carbohydrate group). Among ER-positive tumors (n=18), glutathione was significantly elevated in the carbohydrate group compared to the fasting group (p=0.002), with a positive correlation between preoperative S-insulin levels and the glutathione content in tumors (r=0.680; p=0.002). In all tumors (n=29), glutamate was increased in tumors with high proliferation (t-test; p=0.009), independent of intervention group. Patients with ER-positive / T2 tumors and high tumor glutathione (≥1.09), high S-lactate (≥56.9), and high S-pyruvate (≥12.5) had inferior clinical outcomes regarding relapse-free survival, breast cancer-specific survival, and overall survival. Moreover, Integrated Pathway Analysis (IPA) in serum revealed activation of five major anabolic metabolic networks contributing to proliferation and growth. Conclusions: Preoperative carbohydrate load increases systemic levels of lactate and pyruvate and tumor levels of glutathione and glutamate in ER-positive patients. These biological changes may contribute to the inferior clinical outcomes observed in luminal T2 breast cancer patients. Registration of trial: CliniTrials.gov; NCT03886389. Retrospectively registered March 22, 2019. Available at: https://clinicaltrials.gov/ct2/show/NCT03886389?cond=Breast+cancer+diet&rank=1

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Section: Discussionsupporting

confidence: 64%

“…Metabolites were identified based on previous assignment. [17,18] Twenty-eight metabolites were identified as measurable and their areas calculated by integrating the area under the signal curve.…”

Section: Serum Metabolomics Analysesmentioning

confidence: 99%

Metabolic consequences of perioperative oral carbohydrates in breast cancer patients: An explorative study

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Austdal

Bathen

et al. 2019

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“…Lipids and apolipoproteins associated with LDL and HDL subfractions decreased. Univariate tests also showed significant decreases in TPFC, TPA1, TPA2 and IDAB, in 7, lysine (8), acetate (9), glutamine and glutamate (10), acetoacetate (11), 3-hydroxybutyrate (12), glutamate (13), pyruvate (14), glutamine (15), citrate (16), methionine (17), creatine (18), creatinine (19), ornithine (20), proline betaine (21), dimethyl sulphone (22), unknown (23), histidine (24), glucose (25), glycine (26), lactate (27), tyrosine (28), phenylalanine (29) and formate (30). The figure shows that samples taken after 6 months, having high scores on LV1, have more of the metabolites that are positive on the y-loading axes and less of the negative metabolites, compared to samples taken at baseline addition to significant decreases in lipids and apolipoproteins associated with LDL2 and HDL 2-3, before but not after correction for multiple tests.…”

Section: Metabolic Changes In Patients Not Receiving Chemotherapymentioning

confidence: 93%

“…Metabolic characterization of liquid biopsies, which reflect the systemic effects of the disease and treatment, are gaining increased interest. [15][16][17] The metabolome comprises all low-molecular-weight compounds in the human body, and reflects the dynamic interaction between the individual and the environment. Metabolomics can therefore provide insights into metabolic and physiological changes of pathobiological significance during cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

Metabolite and lipoprotein responses and prediction of weight gain during breast cancer treatment

et al. 2018

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BACKGROUND: Breast cancer treatment has metabolic side effects, potentially affecting risk of cardiovascular disease (CVD) and recurrence. We aimed to compare alterations in serum metabolites and lipoproteins during treatment between recipients and nonrecipients of chemotherapy, and describe metabolite profiles associated with treatment-related weight gain. METHODS: This pilot study includes 60 stage I/II breast cancer patients who underwent surgery and were treated according to national guidelines. Serum sampled pre-surgery and after 6 and 12 months was analysed by MR spectroscopy and mass spectrometry. In all, 170 metabolites and 105 lipoprotein subfractions were quantified. RESULTS: The metabolite and lipoprotein profiles of chemotherapy recipients and non-recipients changed significantly 6 months after surgery (p < 0.001). Kynurenine, the lipid signal at 1.55-1.60 ppm, ADMA, 2 phosphatidylcholines (PC aa C38:3, PC ae C42:1), alpha-aminoadipic acid, hexoses and sphingolipids were increased in chemotherapy recipients after 6 months. VLDL and small dense LDL increased after 6 months, while HDL decreased, with triglyceride enrichment in HDL and LDL. At baseline, weight gainers had less acylcarnitines, phosphatidylcholines, lyso-phosphatidylcholines and sphingolipids, and showed an inflammatory lipid profile. CONCLUSION: Chemotherapy recipients exhibit metabolic changes associated with inflammation, altered immune response and increased risk of CVD. Altered lipid metabolism may predispose for treatment-related weight gain.

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“…Metabolische Profilierung mit NMR in großen epidemiologischen Studien ist zwar noch neu, doch konnten so bereits neue Biomarker für verschiedene Krankheiten entdeckt werden. Es wurden Beiträge zum Verständnis der Ätiologie geleistet und es wurde nachgewiesen, dass man Krankheitsrisiken und die Wirkung von Therapeutika prognostizieren kann – mit dem Potenzial, dies in verschiedenste klinische Situationen zu übertragen …”

Section: Biomedizinische Und Biochemische Signifikanzunclassified

Hochdurchsatz‐Metabolomik mit 1D‐NMR

et al. 2018

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Metabolomik befasst sich mit der Gesamtheit aller Metabolite, dem Metabolom. Als eine der “Omics”‐Wissenschaften hat sie Querbeziehungen zur Biologie, Physiologie, Pathologie und Medizin; andererseits sind Metabolite chemische Verbindungen, kleine organische Moleküle oder anorganische Ionen. Ihre korrekte Identifizierung und Quantifizierung in komplexen biologischen Matrizen erfordert daher eine solide chemische Grundlage. Im Vergleich beispielsweise zu DNA unterliegen Metabolite sehr viel stärker der Oxidation oder dem enzymatischen Abbau: Wir können große Teile eines Mammut‐Genoms aus einer kleinen Probe rekonstruieren, sind aber nicht in der Lage, dasselbe mit seinem Metabolom zu tun, das innerhalb weniger Stunden nach dem Tod des Tieres wahrscheinlich weitgehend abgebaut war. Erforderlich sind daher Standardverfahren, gute chemische Fertigkeiten der Probenvorbereitung für die Lagerung und anschließende Analyse, genaue analytische Protokolle, eine umfangreiche Kenntnis der Chemometrie, erweiterte statistische Verfahren und fundiertes Wissen über mindestens eine der beiden Metabolomik‐typischen Verfahren, MS oder NMR. All diese Fertigkeiten besitzen traditionell die Chemiker. Entsprechend betrachten wir die Metabolomik aus chemischer Perspektive und beschränken uns auf NMR. Der Analytiker findet Argumente für und gegen NMR, jedoch bietet das Verfahren eine besondere ganzheitliche Perspektive, die für künftige Anwendungen als eine bevölkerungsweite Screeningtechnik für Reihenuntersuchungen sprechen.

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NMR‐based metabolomics of biofluids in cancer

Cited by 35 publications

References 120 publications

Metabolic consequences of perioperative oral carbohydrates in breast cancer patients: An explorative study

Metabolic consequences of perioperative oral carbohydrates in breast cancer patients: An explorative study

Metabolite and lipoprotein responses and prediction of weight gain during breast cancer treatment

Hochdurchsatz‐Metabolomik mit 1D‐NMR

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