Abstract
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.
Highlights
Small-intestine (SI) neuroendocrine tumors (NETs) are the most common malignant NETs.small intestine neuroendocrine tumors (SI-NETs) are usually small, multiple in about 30%–50% of cases, and associated with lymph node and liver metastases at diagnosis in more than 90% and 50% of patients, respectively
In the present study, using high-resolution 1H magic angle spinning (HRMAS) nuclear magnetic resonance (NMR) spectroscopy, we have provided the metabolomic profile of primary
46 tissue specimens of ileal neuroendocrine tumors (NETs) obtained from 46 patients who had undergone surgery were retrospectively selected according to the following criteria: (1) final diagnosis according to the pathological standards, (2) absence of both medical and surgical treatment before obtaining the tumor sample for high-resolution 1H magic angle spinning (HRMAS)
Summary
Small-intestine (SI) neuroendocrine tumors (NETs) are the most common malignant NETs. SI-NETs are usually small, multiple in about 30%–50% of cases, and associated with lymph node and liver metastases at diagnosis in more than 90% and 50% of patients, respectively. Well-differentiated NETs constitute a very heterogeneous group, including low-grade tumors that are slowly progressive but able to lead to metastasis or recurrence after treatment, and more aggressive tumors with a rapid rate of progression. Faced with this great diversity of biological behavior, to predict tumor evolution may be very challenging. In patients with no metastatic NETs, it is essential to identify markers able to predict tumor progression; one possible approach is to define the metabolic fingerprint of the tumor compared to normal tissue
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