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

被引：26

作者：

Berchuck, Jacob E. ^{[1
,2
,3
]}

Adib, Elio ^{[1
,2
]}

Abou Alaiwi, Sarah ^{[2
,3
]}

Dash, Amit K. ^{[4
]}

Shin, Jin Na ^{[4
]}

Lowder, Dallin ^{[4
]}

McColl, Collin ^{[4
]}

Castro, Patricia ^{[5
,6
]}

Carelli, Ryan ^{[7
]}

Benedetti, Elisa ^{[7
]}

Deng, Jenny ^{[4
]}

Robertson, Matthew ^{[6
]}

Baca, Sylvan C. ^{[1
,2
]}

Bell, Connor ^{[1
,2
]}

McClure, Heather M. ^{[1
,2
]}

El Zarif, Talal ^{[1
,2
]}

Davidsohn, Matthew P. ^{[1
,2
]}

Lakshminarayanan, Gitanjali ^{[1
,2
]}

Rizwan, Kinza ^{[4
]}

Skapura, Darlene G. ^{[4
]}

Grimm, Sandra L. ^{[6
]}

Davis, Christel M. ^{[8
]}

Ehli, Erik A. ^{[8
]}

Kelleher, Kaitlin M. ^{[1
]}

Seo, Ji-Heui ^{[1
,2
]}

Mitsiades, Nicholas ^{[4
,6
,9
]}

Coarfa, Cristian ^{[6
,9
]}

Pomerantz, Mark M. ^{[1
,2
]}

Loda, Massimo ^{[7
]}

Ittmann, Michael ^{[5
,6
]}

Freedman, Matthew L. ^{[1
,2
,10
]}

Kaochar, Salma ^{[4
,6
,9
,11
]}

机构：

[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA

[2] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA USA

[3] Brigham & Womens Hosp, Dept Med, Boston, MA USA

[4] Baylor Coll Med, Dept Med, Houston, TX USA

[5] Baylor Coll Med, Dept Pathol, Houston, TX USA

[6] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX USA

[7] Avera Inst Human Genet, Sioux Falls, SD USA

[8] Weill Cornell Med, Dept Pathol, Lab Med, New York, NY USA

[9] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX USA

[10] 450 Brookline Ave,Smith 1058, Boston, MA 02215 USA

[11] Baylor Coll Med, 1 Baylor Plaza,New Alkek ABBR R404, Houston, TX 77030 USA

来源：

CANCER RESEARCH | 2022年 / 82卷 / 16期

关键词：

DIFFERENTIALLY METHYLATED GENES; EXPRESSION; TRANSCRIPT; TISSUES; STAGE;

D O I：

10.1158/0008-5472.CAN-21-3552

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：2848 / 2859

页数：12

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