TY - JOUR
T1 - Comparative analysis of 1152 African-American and European-American men with prostate cancer identifies distinct genomic and immunological differences
AU - Rayford, Walter
AU - Beksac, Alp Tuna
AU - Alger, Jordan
AU - Alshalalfa, Mohammed
AU - Ahmed, Mohsen
AU - Khan, Irtaza
AU - Falagario, Ugo G.
AU - Liu, Yang
AU - Davicioni, Elai
AU - Spratt, Daniel E.
AU - Schaeffer, Edward M.
AU - Feng, Felix Y.
AU - Mahal, Brandon
AU - Nguyen, Paul L.
AU - Den, Robert B.
AU - Greenberger, Mark D.
AU - Bradley, Randy
AU - Watson, Justin M.
AU - Beamer, Matthew
AU - Stamatakis, Lambros
AU - Carmen, Darrell J.
AU - Awasthi, Shivanshu
AU - Hwang, Jonathan
AU - Weil, Rachel
AU - Merisaari, Harri
AU - Mohamed, Nihal
AU - Deane, Leslie A.
AU - Chakravarty, Dimple
AU - Yadav, Kamlesh K.
AU - Yamoah, Kosj
AU - Nair, Sujit S.
AU - Tewari, Ashutosh K.
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85107149126&partnerID=8YFLogxK
U2 - 10.1038/s42003-021-02140-y
DO - 10.1038/s42003-021-02140-y
M3 - Article
C2 - 34083737
AN - SCOPUS:85107149126
SN - 2399-3642
VL - 4
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 670
ER -