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Neuroendocrine Neoplasms: Identification of Novel Metabolic Circuits of Potential Diagnostic Utility
SIMPLE SUMMARY: Neuroendocrine neoplasms (NEN) are rare tumours, and currently available, mono-analyte biomarkers for diagnosis and prognosis have poor predictive and prognostic accuracy. Metabolic profiling has been applied to several cancer types, but the systemic metabolic consequences of NEN hav...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864182/ https://www.ncbi.nlm.nih.gov/pubmed/33498434 http://dx.doi.org/10.3390/cancers13030374 |
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author | Jiménez, Beatriz Abellona U, Mei Ran Drymousis, Panagiotis Kyriakides, Michael Clift, Ashley K. Liu, Daniel S. K. Rees, Eleanor Holmes, Elaine Nicholson, Jeremy K. Kinross, James M. Frilling, Andrea |
author_facet | Jiménez, Beatriz Abellona U, Mei Ran Drymousis, Panagiotis Kyriakides, Michael Clift, Ashley K. Liu, Daniel S. K. Rees, Eleanor Holmes, Elaine Nicholson, Jeremy K. Kinross, James M. Frilling, Andrea |
author_sort | Jiménez, Beatriz |
collection | PubMed |
description | SIMPLE SUMMARY: Neuroendocrine neoplasms (NEN) are rare tumours, and currently available, mono-analyte biomarkers for diagnosis and prognosis have poor predictive and prognostic accuracy. Metabolic profiling has been applied to several cancer types, but the systemic metabolic consequences of NEN have not yet been well studied. Here, we demonstrate, in a treatment-naïve cohort of patients with NEN, that several metabolites are dysregulated in NEN and this is detectable in urine, due to changes in cancer metabolic processes, neuroendocrine signalling molecules and the gut mirobiome. This may have relevance for novel diagnostic biomarkers. 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 ((1)H-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 (1)H-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. |
format | Online Article Text |
id | pubmed-7864182 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-78641822021-02-06 Neuroendocrine Neoplasms: Identification of Novel Metabolic Circuits of Potential Diagnostic Utility Jiménez, Beatriz Abellona U, Mei Ran Drymousis, Panagiotis Kyriakides, Michael Clift, Ashley K. Liu, Daniel S. K. Rees, Eleanor Holmes, Elaine Nicholson, Jeremy K. Kinross, James M. Frilling, Andrea Cancers (Basel) Article SIMPLE SUMMARY: Neuroendocrine neoplasms (NEN) are rare tumours, and currently available, mono-analyte biomarkers for diagnosis and prognosis have poor predictive and prognostic accuracy. Metabolic profiling has been applied to several cancer types, but the systemic metabolic consequences of NEN have not yet been well studied. Here, we demonstrate, in a treatment-naïve cohort of patients with NEN, that several metabolites are dysregulated in NEN and this is detectable in urine, due to changes in cancer metabolic processes, neuroendocrine signalling molecules and the gut mirobiome. This may have relevance for novel diagnostic biomarkers. 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 ((1)H-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 (1)H-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. MDPI 2021-01-20 /pmc/articles/PMC7864182/ /pubmed/33498434 http://dx.doi.org/10.3390/cancers13030374 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Jiménez, Beatriz Abellona U, Mei Ran Drymousis, Panagiotis Kyriakides, Michael Clift, Ashley K. Liu, Daniel S. K. Rees, Eleanor Holmes, Elaine Nicholson, Jeremy K. Kinross, James M. Frilling, Andrea Neuroendocrine Neoplasms: Identification of Novel Metabolic Circuits of Potential Diagnostic Utility |
title | Neuroendocrine Neoplasms: Identification of Novel Metabolic Circuits of Potential Diagnostic Utility |
title_full | Neuroendocrine Neoplasms: Identification of Novel Metabolic Circuits of Potential Diagnostic Utility |
title_fullStr | Neuroendocrine Neoplasms: Identification of Novel Metabolic Circuits of Potential Diagnostic Utility |
title_full_unstemmed | Neuroendocrine Neoplasms: Identification of Novel Metabolic Circuits of Potential Diagnostic Utility |
title_short | Neuroendocrine Neoplasms: Identification of Novel Metabolic Circuits of Potential Diagnostic Utility |
title_sort | neuroendocrine neoplasms: identification of novel metabolic circuits of potential diagnostic utility |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864182/ https://www.ncbi.nlm.nih.gov/pubmed/33498434 http://dx.doi.org/10.3390/cancers13030374 |
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