The Prostate Cancer Androgen Receptor Cistrome in African American Men Associates with Upregulation of Lipid Metabolism and Immune Response.
Journal
Cancer research
ISSN: 1538-7445
Titre abrégé: Cancer Res
Pays: United States
ID NLM: 2984705R
Informations de publication
Date de publication:
16 08 2022
16 08 2022
Historique:
received:
19
10
2021
revised:
03
05
2022
accepted:
14
06
2022
pubmed:
23
6
2022
medline:
18
8
2022
entrez:
22
6
2022
Statut:
ppublish
Résumé
African-American (AA) men are more likely to be diagnosed with and die from prostate cancer than European American (EA) men. Despite the central role of the androgen receptor (AR) transcription factor in prostate cancer, little is known about the contribution of epigenetics to observed racial disparities. We performed AR chromatin immunoprecipitation sequencing on primary prostate tumors from AA and EA men, finding that sites with greater AR binding intensity in AA relative to EA prostate cancer are enriched for lipid metabolism and immune response genes. Integration with transcriptomic and metabolomic data demonstrated coinciding upregulation of lipid metabolism gene expression and increased lipid levels in AA prostate cancer. In a metastatic prostate cancer cohort, upregulated lipid metabolism associated with poor prognosis. These findings offer the first insights into ancestry-specific differences in the prostate cancer AR cistrome. The data suggest a model whereby increased androgen signaling may contribute to higher levels of lipid metabolism, immune response, and cytokine signaling in AA prostate tumors. Given the association of upregulated lipogenesis with prostate cancer progression, our study provides a plausible biological explanation for the higher incidence and aggressiveness of prostate cancer observed in AA men. With immunotherapies and inhibitors of metabolic enzymes in clinical development, the altered lipid metabolism and immune response in African-American men provides potential therapeutic opportunities to attenuate racial disparities in prostate cancer.
Identifiants
pubmed: 35731919
pii: 705059
doi: 10.1158/0008-5472.CAN-21-3552
pmc: PMC9379363
mid: NIHMS1820275
doi:
Substances chimiques
Receptors, Androgen
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2848-2859Subventions
Organisme : NCI NIH HHS
ID : U54 CA233223
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA251560
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM136554
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009172
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA131945
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008231
Pays : United States
Informations de copyright
©2022 The Authors; Published by the American Association for Cancer Research.
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