Untargeted lipidomics reveal association of elevated plasma C18 ceramide levels with reduced survival in metastatic castration-resistant prostate cancer patients.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
18 10 2023
18 10 2023
Historique:
received:
16
08
2023
accepted:
04
10
2023
medline:
23
10
2023
pubmed:
19
10
2023
entrez:
18
10
2023
Statut:
epublish
Résumé
Emerging evidence highlights the potential prognostic relevance of circulating lipids in metastatic castration-resistant prostate cancer (mCRPC), with a proposed 3-lipid signature. This study aims to analyze the lipidomic profiles of individuals with mCRPC to identify lipid species that could serve as predictive indicators of prognosis and therapeutic response. Plasma samples were collected from mCRPC patients initiating first-line treatment (1 L) (n = 29) and those previously treated with at least two lines of therapy (> 2 L) (n = 19), including an androgen-receptor signaling inhibitor and a taxane. Employing an untargeted lipidomic approach, lipids were extracted from the plasma samples and subjected to analysis. A comprehensive identification and quantification of 789 plasma lipids was achieved. Notably, 75 species displayed significant dysregulation in > 2 L patients in comparison to the 1 L group. Among these, 63 species exhibited elevated levels, while 12 were reduced. Patients included in > 2 L cohort showed elevated levels of acylcarnitines (CAR), diacylglycerols (DG), phosphatidylethanolamines (PE), triacylglycerols (TG), and ceramides (Cer). Notably, some upregulated lipids, including CAR 14:0, CAR 24:1, Cer d18:1/16:0, Cer d18:1/18:0 (C18 Cer), Cer d18:2/18:0, Cer d18:1/24:1, and Cer d20:1/24:1, showed significant associations with overall survival (OS) in univariate models. Specifically, increased levels of C18 Cer remained significantly associated with poorer OS in the multivariate model, even after adjusting for treatment line and PSA levels (Hazard Ratio: 3.59 [95% Confidence Interval 1.51-8.52], p = 0.004). Employing quantitative mass spectrometry, our findings underscore the independent prognostic significance of C18 Cer in individuals with mCRPC. This discovery opens avenues for further studies within this field.
Identifiants
pubmed: 37853018
doi: 10.1038/s41598-023-44157-9
pii: 10.1038/s41598-023-44157-9
pmc: PMC10585001
doi:
Substances chimiques
Ceramides
0
Androgen Receptor Antagonists
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
17791Informations de copyright
© 2023. Springer Nature Limited.
Références
Nat Rev Urol. 2018 May;15(5):271-286
pubmed: 29460922
Nat Genet. 2018 Feb;50(2):219-228
pubmed: 29335542
PLoS One. 2012;7(11):e48889
pubmed: 23152813
JCO Clin Cancer Inform. 2023 Jul;7:e2300057
pubmed: 37490642
Oncogene. 2018 Feb 8;37(6):710-721
pubmed: 29059155
J Immunol Res. 2018 Apr 4;2018:5808962
pubmed: 29850633
Cancers (Basel). 2022 Sep 30;14(19):
pubmed: 36230715
Cell Oncol (Dordr). 2023 Aug;46(4):825-845
pubmed: 36947340
BMC Med Inform Decis Mak. 2020 Sep 24;20(Suppl 9):223
pubmed: 32967667
Mol Med Rep. 2018 Mar;17(3):4702-4712
pubmed: 29328471
N Engl J Med. 2020 May 28;382(22):2091-2102
pubmed: 32343890
Prostate Cancer Prostatic Dis. 2022 Apr;25(4):641-649
pubmed: 35732821
Adv Cancer Res. 2013;117:37-58
pubmed: 23290776
Int J Mol Sci. 2020 Nov 16;21(22):
pubmed: 33207699
Int J Cancer. 2017 Nov 15;141(10):2112-2120
pubmed: 28741687
J Clin Oncol. 2016 Apr 20;34(12):1402-18
pubmed: 26903579
Cancer Metab. 2020 Jun 19;8:11
pubmed: 32577235
Mol Cancer Ther. 2015 Dec;14(12):2744-52
pubmed: 26494858
Prostate Cancer Prostatic Dis. 2021 Sep;24(3):860-870
pubmed: 33746214
Am J Clin Exp Urol. 2014 Jul 12;2(2):111-20
pubmed: 25374912
Cancers (Basel). 2020 Oct 03;12(10):
pubmed: 33022939
Sci Rep. 2016 Feb 11;6:20984
pubmed: 26865432
Br J Cancer. 2021 Oct;125(9):1185-1196
pubmed: 34262149
Nat Genet. 2018 Feb;50(2):169-171
pubmed: 29335543
Cancers (Basel). 2021 Sep 08;13(18):
pubmed: 34572748
Obesity (Silver Spring). 2015 Jul;23(7):1414-21
pubmed: 25966363
J Clin Endocrinol Metab. 2014 Jan;99(1):E45-52
pubmed: 24243630
ACS Chem Biol. 2015 Jan 16;10(1):225-33
pubmed: 25384187
J Exp Clin Cancer Res. 2019 Nov 12;38(1):464
pubmed: 31718684
Front Oncol. 2021 Jul 27;11:719865
pubmed: 34386430
Cancers (Basel). 2019 Sep 13;11(9):
pubmed: 31540293
Mediators Inflamm. 2017;2017:4806541
pubmed: 29269995
Int J Mol Sci. 2019 May 28;20(11):
pubmed: 31142021
Clin Cancer Res. 2004 Nov 1;10(21):7252-9
pubmed: 15534099
EBioMedicine. 2021 Oct;72:103625
pubmed: 34656931
Cancers (Basel). 2022 Jan 04;14(1):
pubmed: 35008391
Proc Natl Acad Sci U S A. 2019 Jan 8;116(2):631-640
pubmed: 30578319
Cancer Drug Resist. 2022 Aug 2;5(3):846-849
pubmed: 36176749
Atherosclerosis. 2018 Feb;269:159-165
pubmed: 29366988
BMC Med. 2022 Mar 25;20(1):112
pubmed: 35331214
J Oncol. 2020 Sep 7;2020:4986365
pubmed: 32963528
J Steroid Biochem Mol Biol. 2009 Jul;115(3-5):126-36
pubmed: 19442514