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Open AccessArticle

Metabolomics of Small Intestine Neuroendocrine Tumors and Related Hepatic Metastases

Biophysics and Nuclear Medicine, University Hospitals of Strasbourg, 67098 Strasbourg, France
Faculty of Medicine, University of Strasbourg, FMTS, 67000 Strasbourg, France
MNMS Platform, University Hospitals of Strasbourg, 67098 Strasbourg, France
Molecular Imaging—Institut Pluridisciplinaire Hubert Curien (IPHC), UMR 7178 – CNRS/Unistra, 67098 Strasbourg, France
Digestive and Oncologic Surgery, Edouard-Herriot University Hospital, Claude-Bernard Lyon 1 University, 69622 Lyon, France
Hepato-Pancreato-Biliary Surgery and Liver transplantation, University Hospitals of Strasbourg, University of Strasbourg, 67098 Strasbourg, France
INSERM U1052/CNRS UMR5286/University of Lyon, Cancer Research Center of Lyon, 69622 Lyon, France
Computer Engineering Department, Bilkent University, Ankara 06800, Turkey
Pathology, University Hospitals of Strasbourg, Strasbourg University, 67098 Strasbourg, France
Tissu-Tumorothèque Est (CRB-HCL, Hospices Civils de Lyon Biobank, BB-0033-00046), 69622 Lyon, France
Internal Medicine, Diabetes and Metabolic Disorders, University Hospitals of Strasbourg, Strasbourg University, 67098 Strasbourg, France
Medical Oncology, Edouard Herriot Hospital, Hospices Civils de Lyon, 69622 Lyon, France
University of Lyon, Université Lyon 1, 69622 Lyon, France
Author to whom correspondence should be addressed.
Metabolites 2019, 9(12), 300;
Received: 18 November 2019 / Revised: 1 December 2019 / Accepted: 10 December 2019 / Published: 11 December 2019
(This article belongs to the Special Issue Cancer Metabolomics 2019)
To assess the metabolomic fingerprint of small intestine neuroendocrine tumors (SI-NETs) and related hepatic metastases, and to investigate the influence of the hepatic environment on SI-NETs metabolome. Ninety-four tissue samples, including 46 SI-NETs, 18 hepatic NET metastases and 30 normal SI and liver samples, were analyzed using 1H-magic angle spinning (HRMAS) NMR nuclear magnetic resonance (NMR) spectroscopy. Twenty-seven metabolites were identified and quantified. Differences between primary NETs vs. normal SI and primary NETs vs. hepatic metastases, were assessed. Network analysis was performed according to several clinical and pathological features. Succinate, glutathion, taurine, myoinositol and glycerophosphocholine characterized NETs. Normal SI specimens showed higher levels of alanine, creatine, ethanolamine and aspartate. PLS-DA revealed a continuum-like distribution among normal SI, G1-SI-NETs and G2-SI-NETs. The G2-SI-NET distribution was closer and clearly separated from normal SI tissue. Lower concentration of glucose, serine and glycine, and increased levels of choline-containing compounds, taurine, lactate and alanine, were found in SI-NETs with more aggressive tumors. Higher abundance of acetate, succinate, choline, phosphocholine, taurine, lactate and aspartate discriminated liver metastases from normal hepatic parenchyma. Higher levels of alanine, ethanolamine, glycerophosphocholine and glucose was found in hepatic metastases than in primary SI-NETs. The present work gives for the first time a snapshot of the metabolomic characteristics of SI-NETs, suggesting the existence of complex metabolic reality, maybe characteristic of different tumor evolution. View Full-Text
Keywords: neuroendocrine tumors; carcinoid; metabolomics; spectroscopy; NMR neuroendocrine tumors; carcinoid; metabolomics; spectroscopy; NMR
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Imperiale, A.; Poncet, G.; Addeo, P.; Ruhland, E.; Roche, C.; Battini, S.; Cicek, A.E.; Chenard, M.P.; Hervieu, V.; Goichot, B.; Bachellier, P.; Walter, T.; Namer, I.J. Metabolomics of Small Intestine Neuroendocrine Tumors and Related Hepatic Metastases. Metabolites 2019, 9, 300.

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