Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Rayford, Walter, Beksac, Alp Tuna, Alger, Jordan, Alshalalfa, Mohammed, Ahmed, Mohsen, Khan, Irtaza, Falagario, Ugo G., Liu, Yang, Davicioni, Elai, Spratt, Daniel E., Schaeffer, Edward M., Feng, Felix Y., Mahal, Brandon, Nguyen, Paul L., Den, Robert B., Greenberger, Mark D., Bradley, Randy, Watson, Justin M., Beamer, Matthew, Stamatakis, Lambros, Carmen, Darrell J., Awasthi, Shivanshu, Hwang, Jonathan, Weil, Rachel, Merisaari, Harri, Mohamed, Nihal, Deane, Leslie A., Chakravarty, Dimple, Yadav, Kamlesh K., Yamoah, Kosj, Nair, Sujit S., Tewari, Ashutosh K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175556/
https://www.ncbi.nlm.nih.gov/pubmed/34083737
http://dx.doi.org/10.1038/s42003-021-02140-y
_version_ 1783703067558936576
author Rayford, Walter
Beksac, Alp Tuna
Alger, Jordan
Alshalalfa, Mohammed
Ahmed, Mohsen
Khan, Irtaza
Falagario, Ugo G.
Liu, Yang
Davicioni, Elai
Spratt, Daniel E.
Schaeffer, Edward M.
Feng, Felix Y.
Mahal, Brandon
Nguyen, Paul L.
Den, Robert B.
Greenberger, Mark D.
Bradley, Randy
Watson, Justin M.
Beamer, Matthew
Stamatakis, Lambros
Carmen, Darrell J.
Awasthi, Shivanshu
Hwang, Jonathan
Weil, Rachel
Merisaari, Harri
Mohamed, Nihal
Deane, Leslie A.
Chakravarty, Dimple
Yadav, Kamlesh K.
Yamoah, Kosj
Nair, Sujit S.
Tewari, Ashutosh K.
author_facet Rayford, Walter
Beksac, Alp Tuna
Alger, Jordan
Alshalalfa, Mohammed
Ahmed, Mohsen
Khan, Irtaza
Falagario, Ugo G.
Liu, Yang
Davicioni, Elai
Spratt, Daniel E.
Schaeffer, Edward M.
Feng, Felix Y.
Mahal, Brandon
Nguyen, Paul L.
Den, Robert B.
Greenberger, Mark D.
Bradley, Randy
Watson, Justin M.
Beamer, Matthew
Stamatakis, Lambros
Carmen, Darrell J.
Awasthi, Shivanshu
Hwang, Jonathan
Weil, Rachel
Merisaari, Harri
Mohamed, Nihal
Deane, Leslie A.
Chakravarty, Dimple
Yadav, Kamlesh K.
Yamoah, Kosj
Nair, Sujit S.
Tewari, Ashutosh K.
author_sort Rayford, Walter
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8175556
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-81755562021-06-07 Comparative analysis of 1152 African-American and European-American men with prostate cancer identifies distinct genomic and immunological differences Rayford, Walter Beksac, Alp Tuna Alger, Jordan Alshalalfa, Mohammed Ahmed, Mohsen Khan, Irtaza Falagario, Ugo G. Liu, Yang Davicioni, Elai Spratt, Daniel E. Schaeffer, Edward M. Feng, Felix Y. Mahal, Brandon Nguyen, Paul L. Den, Robert B. Greenberger, Mark D. Bradley, Randy Watson, Justin M. Beamer, Matthew Stamatakis, Lambros Carmen, Darrell J. Awasthi, Shivanshu Hwang, Jonathan Weil, Rachel Merisaari, Harri Mohamed, Nihal Deane, Leslie A. Chakravarty, Dimple Yadav, Kamlesh K. Yamoah, Kosj Nair, Sujit S. Tewari, Ashutosh K. Commun Biol Article 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. Nature Publishing Group UK 2021-06-03 /pmc/articles/PMC8175556/ /pubmed/34083737 http://dx.doi.org/10.1038/s42003-021-02140-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Rayford, Walter
Beksac, Alp Tuna
Alger, Jordan
Alshalalfa, Mohammed
Ahmed, Mohsen
Khan, Irtaza
Falagario, Ugo G.
Liu, Yang
Davicioni, Elai
Spratt, Daniel E.
Schaeffer, Edward M.
Feng, Felix Y.
Mahal, Brandon
Nguyen, Paul L.
Den, Robert B.
Greenberger, Mark D.
Bradley, Randy
Watson, Justin M.
Beamer, Matthew
Stamatakis, Lambros
Carmen, Darrell J.
Awasthi, Shivanshu
Hwang, Jonathan
Weil, Rachel
Merisaari, Harri
Mohamed, Nihal
Deane, Leslie A.
Chakravarty, Dimple
Yadav, Kamlesh K.
Yamoah, Kosj
Nair, Sujit S.
Tewari, Ashutosh K.
Comparative analysis of 1152 African-American and European-American men with prostate cancer identifies distinct genomic and immunological differences
title Comparative analysis of 1152 African-American and European-American men with prostate cancer identifies distinct genomic and immunological differences
title_full Comparative analysis of 1152 African-American and European-American men with prostate cancer identifies distinct genomic and immunological differences
title_fullStr Comparative analysis of 1152 African-American and European-American men with prostate cancer identifies distinct genomic and immunological differences
title_full_unstemmed Comparative analysis of 1152 African-American and European-American men with prostate cancer identifies distinct genomic and immunological differences
title_short Comparative analysis of 1152 African-American and European-American men with prostate cancer identifies distinct genomic and immunological differences
title_sort comparative analysis of 1152 african-american and european-american men with prostate cancer identifies distinct genomic and immunological differences
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175556/
https://www.ncbi.nlm.nih.gov/pubmed/34083737
http://dx.doi.org/10.1038/s42003-021-02140-y
work_keys_str_mv AT rayfordwalter comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT beksacalptuna comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT algerjordan comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT alshalalfamohammed comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT ahmedmohsen comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT khanirtaza comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT falagariougog comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT liuyang comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT davicionielai comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT sprattdaniele comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT schaefferedwardm comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT fengfelixy comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT mahalbrandon comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT nguyenpaull comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT denrobertb comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT greenbergermarkd comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT bradleyrandy comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT watsonjustinm comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT beamermatthew comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT stamatakislambros comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT carmendarrellj comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT awasthishivanshu comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT hwangjonathan comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT weilrachel comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT merisaariharri comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT mohamednihal comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT deanelesliea comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT chakravartydimple comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT yadavkamleshk comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT yamoahkosj comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT nairsujits comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences
AT tewariashutoshk comparativeanalysisof1152africanamericanandeuropeanamericanmenwithprostatecanceridentifiesdistinctgenomicandimmunologicaldifferences