The Prostate Cancer Androgen Receptor Cistrome in African American Men Associates with Upregulation of Lipid Metabolism and Immune Response.

Autor:	Berchuck JE; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts., Adib E; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts., Abou Alaiwi S; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts., Dash AK; Department of Medicine, Baylor College of Medicine, Houston, Texas., Shin JN; Department of Medicine, Baylor College of Medicine, Houston, Texas., Lowder D; Department of Medicine, Baylor College of Medicine, Houston, Texas., McColl C; Department of Medicine, Baylor College of Medicine, Houston, Texas., Castro P; Department of Pathology, Baylor College of Medicine, Houston, Texas.; Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, Texas., Carelli R; Avera Institute for Human Genetics, Sioux Falls, South Dakota., Benedetti E; Avera Institute for Human Genetics, Sioux Falls, South Dakota., Deng J; Department of Medicine, Baylor College of Medicine, Houston, Texas., Robertson M; Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, Texas., Baca SC; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts., Bell C; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts., McClure HM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts., El Zarif T; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts., Davidsohn MP; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts., Lakshminarayanan G; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts., Rizwan K; Department of Medicine, Baylor College of Medicine, Houston, Texas., Skapura DG; Department of Medicine, Baylor College of Medicine, Houston, Texas., Grimm SL; Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, Texas., Davis CM; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York., Ehli EA; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York., Kelleher KM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts., Seo JH; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts., Mitsiades N; Department of Medicine, Baylor College of Medicine, Houston, Texas.; Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, Texas.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas., Coarfa C; Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, Texas.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas., Pomerantz MM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts., Loda M; Avera Institute for Human Genetics, Sioux Falls, South Dakota., Ittmann M; Department of Pathology, Baylor College of Medicine, Houston, Texas.; Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, Texas., Freedman ML; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts., Kaochar S; Department of Medicine, Baylor College of Medicine, Houston, Texas.; Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, Texas.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas.
Jazyk:	angličtina
Zdroj:	Cancer research [Cancer Res] 2022 Aug 16; Vol. 82 (16), pp. 2848-2859.
DOI:	10.1158/0008-5472.CAN-21-3552
Abstrakt:	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. Significance: 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. (©2022 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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