Comprehensive plasma steroidomics reveals subtle alterations of systemic steroid profile in patients at different stages of prostate cancer disease.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
18 01 2024
18 01 2024
Historique:
received:
25
09
2023
accepted:
10
01
2024
medline:
19
1
2024
pubmed:
19
1
2024
entrez:
18
1
2024
Statut:
epublish
Résumé
The steroid submetabolome, or steroidome, is of particular interest in prostate cancer (PCa) as the dependence of PCa growth on androgens is well known and has been routinely exploited in treatment for decades. Nevertheless, the community is still far from a comprehensive understanding of steroid involvement in PCa both at the tissue and at systemic level. In this study we used liquid chromatography/high resolution mass spectrometry (LC/HRMS) backed by a dynamic retention time database DynaSTI to obtain a readout on circulating steroids in a cohort reflecting a progression of the PCa. Hence, 60 relevant compounds were annotated in the resulting LC/HRMS data, including 22 unknown steroid isomers therein. Principal component analysis revealed only subtle alterations of the systemic steroidome in the study groups. Next, a supervised approach allowed for a differentiation between the healthy state and any of the stages of the disease. Subsequent clustering of steroid metabolites revealed two groups responsible for this outcome: one consisted primarily of the androgens, whereas another contained corticosterone and its metabolites. The androgen data supported the currently established involvement of a hypothalamic-pituitary-gonadal axis in the development of PCa, whereas biological role of corticosterone remained elusive. On top of that, current results suggested a need for improvement in the dynamic range of the analytical methods to better understand the role of low abundant steroids, as the analysis revealed an involvement of estrogen metabolites. In particular, 2-hydroxyestradiol-3-methylether, one of the compounds present in the disease phenotype, was annotated and reported for the first time in men.
Identifiants
pubmed: 38238434
doi: 10.1038/s41598-024-51859-1
pii: 10.1038/s41598-024-51859-1
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1577Informations de copyright
© 2024. The Author(s).
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