Neuroendocrine Neoplasms: Identification of Novel Metabolic Circuits of Potential Diagnostic Utility
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 (<sup...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/3/374 |
| _version_ | 1797409278145855488 |
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| author | Beatriz Jiménez Mei Ran Abellona U Panagiotis Drymousis Michael Kyriakides Ashley K. Clift Daniel S. K. Liu Eleanor Rees Elaine Holmes Jeremy K. Nicholson James M. Kinross Andrea Frilling |
| author_facet | Beatriz Jiménez Mei Ran Abellona U Panagiotis Drymousis Michael Kyriakides Ashley K. Clift Daniel S. K. Liu Eleanor Rees Elaine Holmes Jeremy K. Nicholson James M. Kinross Andrea Frilling |
| author_sort | Beatriz Jiménez |
| collection | DOAJ |
| description | 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 (<sup>1</sup>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 <sup>1</sup>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-<i>N</i>-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. |
| first_indexed | 2024-03-09T04:11:54Z |
| format | Article |
| id | doaj.art-a82909968f3c4ccb90a3a432d2ddcd48 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T04:11:54Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-a82909968f3c4ccb90a3a432d2ddcd482023-12-03T13:58:58ZengMDPI AGCancers2072-66942021-01-0113337410.3390/cancers13030374Neuroendocrine Neoplasms: Identification of Novel Metabolic Circuits of Potential Diagnostic UtilityBeatriz Jiménez0Mei Ran Abellona U1Panagiotis Drymousis2Michael Kyriakides3Ashley K. Clift4Daniel S. K. Liu5Eleanor Rees6Elaine Holmes7Jeremy K. Nicholson8James M. Kinross9Andrea Frilling10Department of Surgery and Cancer, Imperial College London, Exhibition Road, London SW7 2AZ, UKDepartment of Surgery and Cancer, Imperial College London, Exhibition Road, London SW7 2AZ, UKDepartment of Surgery and Cancer, Imperial College London, Exhibition Road, London SW7 2AZ, UKDepartment of Surgery and Cancer, Imperial College London, Exhibition Road, London SW7 2AZ, UKDepartment of Surgery and Cancer, Imperial College London, Exhibition Road, London SW7 2AZ, UKDepartment of Surgery and Cancer, Imperial College London, Exhibition Road, London SW7 2AZ, UKDepartment of Surgery and Cancer, Imperial College London, Exhibition Road, London SW7 2AZ, UKDepartment of Metabolism, Nutrition and Reproduction, Imperial College London, Exhibition Road, London SW7 2AZ, UKThe Australian National Phenome Centre, Health Futures Institute, Murdoch University, Perth 6150, AustraliaDepartment of Surgery and Cancer, Imperial College London, Exhibition Road, London SW7 2AZ, UKDepartment of Surgery and Cancer, Imperial College London, Exhibition Road, London SW7 2AZ, UKThe 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 (<sup>1</sup>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 <sup>1</sup>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-<i>N</i>-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.https://www.mdpi.com/2072-6694/13/3/374neuroendocrine neoplasmsneuroendocrine tumoursbiomarkersnuclear magnetic resonancemetabolic profilingmetabonomics |
| spellingShingle | Beatriz Jiménez Mei Ran Abellona U Panagiotis Drymousis Michael Kyriakides Ashley K. Clift Daniel S. K. Liu Eleanor Rees Elaine Holmes Jeremy K. Nicholson James M. Kinross Andrea Frilling Neuroendocrine Neoplasms: Identification of Novel Metabolic Circuits of Potential Diagnostic Utility Cancers neuroendocrine neoplasms neuroendocrine tumours biomarkers nuclear magnetic resonance metabolic profiling metabonomics |
| 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 | neuroendocrine neoplasms neuroendocrine tumours biomarkers nuclear magnetic resonance metabolic profiling metabonomics |
| url | https://www.mdpi.com/2072-6694/13/3/374 |
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