Comprehensive Plasma Metabolomic Profile of Patients with Advanced Neuroendocrine Tumors (NETs). Diagnostic and Biological Relevance.
NETs
diagnostic biomarkers
disease modelling
machine learning
metabolic signaling
molecular pathways
plasma metabolites
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
27 May 2021
27 May 2021
Historique:
received:
29
04
2021
revised:
19
05
2021
accepted:
20
05
2021
entrez:
2
6
2021
pubmed:
3
6
2021
medline:
3
6
2021
Statut:
epublish
Résumé
High-throughput "-omic" technologies have enabled the detailed analysis of metabolic networks in several cancers, but NETs have not been explored to date. We aim to assess the metabolomic profile of NET patients to understand metabolic deregulation in these tumors and identify novel biomarkers with clinical potential. Plasma samples from 77 NETs and 68 controls were profiled by GC-MS, CE-MS and LC-MS untargeted metabolomics. OPLS-DA was performed to evaluate metabolomic differences. Related pathways were explored using Metaboanalyst 4.0. Finally, ROC and OPLS-DA analyses were performed to select metabolites with biomarker potential. We identified 155 differential compounds between NETs and controls. We have detected an increase of bile acids, sugars, oxidized lipids and oxidized products from arachidonic acid and a decrease of carnitine levels in NETs. MPA/MSEA identified 32 enriched metabolic pathways in NETs related with the TCA cycle and amino acid metabolism. Finally, OPLS-DA and ROC analysis revealed 48 metabolites with diagnostic potential. This study provides, for the first time, a comprehensive metabolic profile of NET patients and identifies a distinctive metabolic signature in plasma of potential clinical use. A reduced set of metabolites of high diagnostic accuracy has been identified. Additionally, new enriched metabolic pathways annotated may open innovative avenues of clinical research.
Identifiants
pubmed: 34072010
pii: cancers13112634
doi: 10.3390/cancers13112634
pmc: PMC8197817
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : PFIZER/GETNE
ID : G1808
Organisme : MICINN and FEDER Funding
ID : RTI2018-095166-B-I00
Organisme : Autonomous Community of Madrid
ID : NOVELREN-CM. Ref: B2017/BMD3751
Organisme : AECC
ID : POSTDO46SOLD
Organisme : CEU-International Doctoral School (CEINDO)
ID : Unknown
Organisme : Autonomous Community of Madrid
ID : PEJD-2019-PRE/BMD-17058, Progama de Empleo Juvenil (YEI), co-funded by European Union (ERDF/ESF, "Investing in your future").
Organisme : Autonomous Community of Madrid
ID : PEJD-2016-PRE/BMD-2666
Organisme : Autonomous Community of Madrid
ID : PEJD-2017-PRE/BMD-4981
Organisme : Instituto de Salud Carlos III
ID : Rio Hortega
Organisme : AECC
ID : CLSEN19003RIES
Références
Clin Genet. 2012 Dec;82(6):558-63
pubmed: 22035404
Nature. 2017 Jul 6;547(7661):109-113
pubmed: 28658205
Cancer Metastasis Rev. 2018 Sep;37(2-3):237-243
pubmed: 30078159
Nucleic Acids Res. 2014 Jan;42(Database issue):D199-205
pubmed: 24214961
Nat Metab. 2020 Feb;2(2):132-141
pubmed: 32694690
Clin Transl Oncol. 2019 Jan;21(1):55-63
pubmed: 30535553
Surgery. 2013 Dec;154(6):1185-92; discussion 1192-3
pubmed: 24383116
Nucleic Acids Res. 2014 Jan;42(Database issue):D478-84
pubmed: 24203708
Biochem Med (Zagreb). 2016 Oct 15;26(3):297-307
pubmed: 27812299
J Clin Endocrinol Metab. 2001 Dec;86(12):5658-71
pubmed: 11739416
Nat Rev Cancer. 2004 Oct;4(10):781-92
pubmed: 15510159
Lancet. 2016 Mar 5;387(10022):968-977
pubmed: 26703889
Nature. 2017 Mar 2;543(7643):65-71
pubmed: 28199314
Nature. 2011 Aug 31;477(7362):54-60
pubmed: 21886157
J Proteomics. 2014 May 30;103:57-71
pubmed: 24698665
Metabolites. 2019 Apr 26;9(5):
pubmed: 31035489
Anal Chem. 2020 Apr 7;92(7):4848-4857
pubmed: 32119527
Hum Pathol. 2003 Jan;34(1):18-27
pubmed: 12605362
Science. 2011 Mar 4;331(6021):1199-203
pubmed: 21252315
Cancer Res. 2012 Jan 1;72(1):356-64
pubmed: 22080567
Nat Rev Cancer. 2016 Nov;16(11):680-693
pubmed: 27658530
N Engl J Med. 2011 Feb 10;364(6):514-23
pubmed: 21306238
JAMA Oncol. 2017 Oct 1;3(10):1335-1342
pubmed: 28448665
Oncologist. 2018 Apr;23(4):422-432
pubmed: 29330208
Int J Mol Sci. 2018 Mar 06;19(3):
pubmed: 29509701
Metab Eng. 2017 Sep;43(Pt B):198-207
pubmed: 27856334
Anal Bioanal Chem. 2013 May;405(14):4849-58
pubmed: 23535741
Mol Cell Endocrinol. 2014 Apr 5;386(1-2):2-15
pubmed: 23933118
Endocrinol Metab Clin North Am. 2018 Sep;47(3):525-548
pubmed: 30098714
Protein Cell. 2018 Feb;9(2):216-237
pubmed: 28748451
Dis Model Mech. 2018 Aug 6;11(8):
pubmed: 30082427
Oncology. 2000 Nov;59(4):269-82
pubmed: 11096338
Clin Cancer Res. 2016 Jan 1;22(1):250-8
pubmed: 26169971
Genet Med. 2010 Jan;12(1):1-11
pubmed: 20027112
Cell Metab. 2017 Jan 10;25(1):43-56
pubmed: 28094011
Nat Rev Cancer. 2011 Feb;11(2):85-95
pubmed: 21258394
Clin Cancer Res. 2017 Jun 15;23(12):e68-e75
pubmed: 28620007
Cancer Res Treat. 2015 Jan;47(1):78-89
pubmed: 25143052
Clin Pharmacokinet. 2012 Sep 1;51(9):553-72
pubmed: 22804748
J Pharm Biomed Anal. 2018 May 30;154:138-149
pubmed: 29547800
Sci Rep. 2019 Dec 27;9(1):20198
pubmed: 31882610
Cancers (Basel). 2019 Oct 10;11(10):
pubmed: 31658655
Ann Oncol. 2011 Jun;22(6):1295-1301
pubmed: 21199886
Cancers (Basel). 2019 Aug 04;11(8):
pubmed: 31382663
Biochim Biophys Acta. 2015 Apr;1851(4):340-55
pubmed: 25449650
Clin Cancer Res. 2019 Aug 15;25(16):5107-5121
pubmed: 31164374
Endocr Rev. 2020 Apr 1;41(2):
pubmed: 31555796
J Chromatogr B Analyt Technol Biomed Life Sci. 2019 Jul 1;1120:62-70
pubmed: 31071580
Metabolites. 2019 Dec 11;9(12):
pubmed: 31835679
J Biomed Sci. 2015 Mar 21;22:22
pubmed: 25885228
Mol Biosyst. 2013 Nov;9(11):2589-96
pubmed: 23999822
J Pharm Biomed Anal. 2014 Nov;100:369-380
pubmed: 25213261
Curr Protoc Bioinformatics. 2019 Dec;68(1):e86
pubmed: 31756036
J Chromatogr A. 2020 Aug 16;1625:461233
pubmed: 32709312
J Lipid Res. 2009 Apr;50 Suppl:S9-14
pubmed: 19098281