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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
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 |