Imperial College London
Alternate

Emeritus ProfessorJeremyNicholson

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Emeritus Professor of Biological Chemistry
 
 
 
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Contact

 

+44 (0)20 7594 3195j.nicholson Website

 
 
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Assistant

 

Ms Wendy Torto +44 (0)20 7594 3225

 
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Location

 

Office no. 665Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Jimenez:2021:10.3390/cancers13030374,
author = {Jimenez, B and Abellona, MRU and Drymousis, P and Kyriakides, M and Clift, AK and Liu, DSK and Rees, E and Holmes, E and Nicholson, JK and Kinross, JM and Frilling, A},
doi = {10.3390/cancers13030374},
journal = {Cancers},
title = {Neuroendocrine neoplasms: identification of novel metabolic circuits of potential diagnostic utility},
url = {http://dx.doi.org/10.3390/cancers13030374},
volume = {13},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Jimenez,B
AU  - Abellona,MRU
AU  - Drymousis,P
AU  - Kyriakides,M
AU  - Clift,AK
AU  - Liu,DSK
AU  - Rees,E
AU  - Holmes,E
AU  - Nicholson,JK
AU  - Kinross,JM
AU  - Frilling,A
DO  - 10.3390/cancers13030374
PY  - 2021///
SN  - 2072-6694
TI  - Neuroendocrine neoplasms: identification of novel metabolic circuits of potential diagnostic utility
T2  - Cancers
UR  - http://dx.doi.org/10.3390/cancers13030374
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000614982900001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/86902
VL  - 13
ER  -
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