Neuroendocrine Neoplasms: Identification Of Novel Metabolic Circuits of Potential Diagnostic Utility

Cancers

AshleyK. Clift¹  Beatriz Jiménez¹  Michael Kyriakides¹  Eleanor Rees¹  DanielS. K. Liu¹  MeiRan Abellona U¹  JamesM. Kinross¹  Andrea Frilling¹  Panagiotis Drymousis¹  Elaine Holmes²  JeremyK. Nicholson² 

[1] Department of Surgery and Cancer, Imperial College London, Exhibition Road, London SW7 2AZ, UK;The Australian National Phenome Centre, Health Futures Institute, Murdoch University, Perth 6150, Australia;

关键词: neuroendocrine neoplasms;    neuroendocrine tumours;    biomarkers;    nuclear magnetic resonance;    metabolic profiling;    metabonomics;   

DOI  :  10.3390/cancers13030374

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown