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Neuroendocrine neoplasms: identification of novel metabolic circuits of potential diagnostic utility

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Title: Neuroendocrine neoplasms: identification of novel metabolic circuits of potential diagnostic utility
Authors: Jimenez, B
Abellona, MRU
Drymousis, P
Kyriakides, M
Clift, AK
Liu, DSK
Rees, E
Holmes, E
Nicholson, JK
Kinross, JM
Frilling, A
Item Type: Journal Article
Abstract: The incidence of neuroendocrine neoplasms (NEN) is increasing, but established biomarkers have poor diagnostic and prognostic accuracy. Here, we aim to define the systemic metabolic consequences of NEN and to establish the diagnostic utility of proton nuclear magnetic resonance spectroscopy (1H-NMR) for NEN in a prospective cohort of patients through a single-centre, prospective controlled observational study. Urine samples of 34 treatment-naïve NEN patients (median age: 59.3 years, range: 36–85): 18 had pancreatic (Pan) NEN, of which seven were functioning; 16 had small bowel (SB) NEN; 20 age- and sex-matched healthy control individuals were analysed using a 600 MHz Bruker 1H-NMR spectrometer. Orthogonal partial-least-squares-discriminant analysis models were able to discriminate both PanNEN and SBNEN patients from healthy control (Healthy vs. PanNEN: AUC = 0.90, Healthy vs. SBNEN: AUC = 0.90). Secondary metabolites of tryptophan, such as trigonelline and a niacin-related metabolite were also identified to be universally decreased in NEN patients, while upstream metabolites, such as kynurenine, were elevated in SBNEN. Hippurate, a gut-derived metabolite, was reduced in all patients, whereas other gut microbial co-metabolites, trimethylamine-N-oxide, 4-hydroxyphenylacetate and phenylacetylglutamine, were elevated in those with SBNEN. These findings suggest the existence of a new systems-based neuroendocrine circuit, regulated in part by cancer metabolism, neuroendocrine signalling molecules and gut microbial co-metabolism. Metabonomic profiling of NEN has diagnostic potential and could be used for discovering biomarkers for these tumours. These preliminary data require confirmation in a larger cohort.
Issue Date: 1-Feb-2021
Date of Acceptance: 14-Jan-2021
URI: http://hdl.handle.net/10044/1/86902
DOI: 10.3390/cancers13030374
ISSN: 2072-6694
Publisher: MDPI AG
Journal / Book Title: Cancers
Volume: 13
Issue: 3
Copyright Statement: © 2021 by the authors.Licensee MDPI, Basel, Switzerland.This article is an open access articledistributed under the terms andconditions of the Creative CommonsAttribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
neuroendocrine neoplasms
neuroendocrine tumours
biomarkers
nuclear magnetic resonance
metabolic profiling
metabonomics
precision medicine
biomarkers
metabolic profiling
metabonomics
neuroendocrine neoplasms
neuroendocrine tumours
nuclear magnetic resonance
precision medicine
Science & Technology
Life Sciences & Biomedicine
Oncology
neuroendocrine neoplasms
neuroendocrine tumours
biomarkers
nuclear magnetic resonance
metabolic profiling
metabonomics
precision medicine
1112 Oncology and Carcinogenesis
Publication Status: Published
Article Number: ARTN 374
Appears in Collections:Department of Metabolism, Digestion and Reproduction
Department of Surgery and Cancer



This item is licensed under a Creative Commons License Creative Commons