Comparative analysis of 1152 African-American and European-American men with prostate cancer identifies distinct genomic and immunological differences.


Journal

Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179

Informations de publication

Date de publication:
03 06 2021
Historique:
received: 01 11 2019
accepted: 15 04 2021
entrez: 4 6 2021
pubmed: 5 6 2021
medline: 17 8 2021
Statut: epublish

Résumé

Racial disparities in prostate cancer have not been well characterized on a genomic level. Here we show the results of a multi-institutional retrospective analysis of 1,152 patients (596 African-American men (AAM) and 556 European-American men (EAM)) who underwent radical prostatectomy. Comparative analyses between the race groups were conducted at the clinical, genomic, pathway, molecular subtype, and prognostic levels. The EAM group had increased ERG (P < 0.001) and ETS (P = 0.02) expression, decreased SPINK1 expression (P < 0.001), and basal-like (P < 0.001) molecular subtypes. After adjusting for confounders, the AAM group was associated with higher expression of CRYBB2, GSTM3, and inflammation genes (IL33, IFNG, CCL4, CD3, ICOSLG), and lower expression of mismatch repair genes (MSH2, MSH6) (p < 0.001 for all). At the pathway level, the AAM group had higher expression of genes sets related to the immune response, apoptosis, hypoxia, and reactive oxygen species. EAM group was associated with higher levels of fatty acid metabolism, DNA repair, and WNT/beta-catenin signaling. Based on cell lines data, AAM were predicted to have higher potential response to DNA damage. In conclusion, biological characteristics of prostate tumor were substantially different in AAM when compared to EAM.

Identifiants

pubmed: 34083737
doi: 10.1038/s42003-021-02140-y
pii: 10.1038/s42003-021-02140-y
pmc: PMC8175556
doi:

Banques de données

ClinicalTrials.gov
['NCT02609269']

Types de publication

Comparative Study Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

670

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Auteurs

Walter Rayford (W)

The Urology Group LLC, Memphis, TN, USA.

Alp Tuna Beksac (AT)

Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Jordan Alger (J)

Department of Urology, Medstar Georgetown University Hospital, Washington, DC, USA.

Mohammed Alshalalfa (M)

Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.

Mohsen Ahmed (M)

Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Irtaza Khan (I)

Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Ugo G Falagario (UG)

Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Yang Liu (Y)

Decipher Biosciences, San Diego, CA, USA.

Elai Davicioni (E)

Decipher Biosciences, San Diego, CA, USA.

Daniel E Spratt (DE)

Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.

Edward M Schaeffer (EM)

Department of Urology, Northwestern University, Chicago, IL, USA.

Felix Y Feng (FY)

Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.

Brandon Mahal (B)

Department of Radiation Oncology, Brigham and Women's Hospital, Boston, MA, USA.

Paul L Nguyen (PL)

Department of Radiation Oncology, Brigham and Women's Hospital, Boston, MA, USA.

Robert B Den (RB)

Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, USA.

Mark D Greenberger (MD)

The Urology Group LLC, Memphis, TN, USA.

Randy Bradley (R)

Haslam College of Business, University of Tennessee, Knoxville, TN, USA.

Justin M Watson (JM)

WellStar Urology, Marietta, GA, USA.

Matthew Beamer (M)

Department of Urology, Medstar Georgetown University Hospital, Washington, DC, USA.

Lambros Stamatakis (L)

Department of Urology, Medstar Georgetown University Hospital, Washington, DC, USA.

Darrell J Carmen (DJ)

Georgia Urology, Atlanta, GA, USA.

Shivanshu Awasthi (S)

Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL, USA.

Jonathan Hwang (J)

Department of Urology, Medstar Georgetown University Hospital, Washington, DC, USA.

Rachel Weil (R)

Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Harri Merisaari (H)

Department of Clinical Medicine, University of Turku, Turku, Finland.

Nihal Mohamed (N)

Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Leslie A Deane (LA)

Department of Urology, Rush University Medical Center, Chicago, IL, USA.

Dimple Chakravarty (D)

Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Kamlesh K Yadav (KK)

Sema4, a Mount Sinai venture, Stamford, CT, USA.

Kosj Yamoah (K)

Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL, USA.

Sujit S Nair (SS)

Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Ashutosh K Tewari (AK)

Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. ash.tewari@mountsinai.org.

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