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.

中文翻译：

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小肠神经内分泌肿瘤和相关肝转移的代谢组学。

评估小肠神经内分泌肿瘤（SI-NETs）和相关肝转移的代谢组学指纹，并研究肝环境对SI-NETs代谢组的影响。使用1H-磁角旋转（HRMAS）NMR核磁共振（NMR）光谱分析了94个组织样本，包括46个SI-NET，18个肝NET转移灶和30个正常SI和肝样本。鉴定并量化了27种代谢物。评估了原发性NET与正常SI之间以及原发性NET与肝转移之间的差异。根据一些临床和病理特征进行了网络分析。琥珀酸，谷胱甘肽，牛磺酸，肌醇和甘油磷酸胆碱为NETs。正常的SI标本显示出较高水平的丙氨酸，肌酸，乙醇胺和天冬氨酸。PLS-DA揭示了正常SI，G1-SI-NET和G2-SI-NET之间的连续体状分布。G2-SI-NET的分布与正常的SI组织更加接近且明显分开。在具有更具侵略性的肿瘤的SI-NET中发现较低的葡萄糖，丝氨酸和甘氨酸浓度，以及增加的含胆碱化合物（牛磺酸，乳酸和丙氨酸）水平。乙酸，琥珀酸，胆碱，磷酸胆碱，牛磺酸，乳酸和天门冬氨酸的丰度较高，可将肝转移与正常肝实质区别开来。与原发性SI-NET相比，肝转移中发现的丙氨酸，乙醇胺，甘油磷酸胆碱和葡萄糖水平更高。本工作首次给出了SI-NETs代谢组学特征的快照，表明存在复杂的代谢现实，可能是不同肿瘤演变的特征。