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Integrative comparison of the genomic and transcriptomic landscape between prostate cancer patients of predominantly African or European genetic ancestry

Men of predominantly African Ancestry (AA) have higher prostate cancer (CaP) incidence and worse survival than men of predominantly European Ancestry (EA). While socioeconomic factors drive this disparity, genomic factors may also contribute to differences in the incidence and mortality rates. To co...

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Autores principales: Yuan, Jiao, Kensler, Kevin H., Hu, Zhongyi, Zhang, Youyou, Zhang, Tianli, Jiang, Junjie, Xu, Mu, Pan, Yutian, Long, Meixiao, Montone, Kathleen T., Tanyi, Janos L., Fan, Yi, Zhang, Rugang, Hu, Xiaowen, Rebbeck, Timothy R., Zhang, Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046294/
https://www.ncbi.nlm.nih.gov/pubmed/32059012
http://dx.doi.org/10.1371/journal.pgen.1008641
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author Yuan, Jiao
Kensler, Kevin H.
Hu, Zhongyi
Zhang, Youyou
Zhang, Tianli
Jiang, Junjie
Xu, Mu
Pan, Yutian
Long, Meixiao
Montone, Kathleen T.
Tanyi, Janos L.
Fan, Yi
Zhang, Rugang
Hu, Xiaowen
Rebbeck, Timothy R.
Zhang, Lin
author_facet Yuan, Jiao
Kensler, Kevin H.
Hu, Zhongyi
Zhang, Youyou
Zhang, Tianli
Jiang, Junjie
Xu, Mu
Pan, Yutian
Long, Meixiao
Montone, Kathleen T.
Tanyi, Janos L.
Fan, Yi
Zhang, Rugang
Hu, Xiaowen
Rebbeck, Timothy R.
Zhang, Lin
author_sort Yuan, Jiao
collection PubMed
description Men of predominantly African Ancestry (AA) have higher prostate cancer (CaP) incidence and worse survival than men of predominantly European Ancestry (EA). While socioeconomic factors drive this disparity, genomic factors may also contribute to differences in the incidence and mortality rates. To compare the prevalence of prostate tumor genomic alterations and transcriptomic profiles by patient genetic ancestry, we evaluated genomic profiles from The Cancer Genome Atlas (TCGA) CaP cohort (n = 498). Patient global and local genetic ancestry were estimated by computational algorithms using genotyping data; 414 (83.1%) were EA, 61 (12.2%) were AA, 11 (2.2%) were East Asian Ancestry (EAA), 10 (2.0%) were Native American (NA), and 2 (0.4%) were other ancestry. Genetic ancestry was highly concordant with self-identified race/ethnicity. Subsequent analyses were limited to 61 AA and 414 EA cases. Significant differences were observed by ancestry in the frequency of SPOP mutations (20.3% AA vs. 10.0% EA; p = 5.6×10(−03)), TMPRSS2-ERG fusions (29.3% AA vs. 39.6% EA; p = 4.4×10(−02)), and PTEN deletions/losses (11.5% AA vs. 30.2% EA; p = 3.5×10(−03)). Differentially expressed genes (DEGs) between AAs and EAs showed significant enrichment for prostate eQTL target genes (p = 8.09×10(−48)). Enrichment of highly expressed DEGs for immune-related pathways was observed in AAs, and for PTEN/PI3K signaling in EAs. Nearly one-third of DEGs (31.3%) were long non-coding RNAs (DE-lncRNAs). The proportion of DE-lncRNAs with higher expression in AAs greatly exceeded that with lower expression in AAs (p = 1.2×10(−125)). Both ChIP-seq and RNA-seq data suggested a stronger regulatory role for AR signaling pathways in DE-lncRNAs vs. non-DE-lncRNAs. CaP-related oncogenic lncRNAs, such as PVT1, PCAT1 and PCAT10/CTBP1-AS, were found to be more highly expressed in AAs. We report substantial heterogeneity in the prostate tumor genome and transcriptome between EA and AA. These differences may be biological contributors to racial disparities in CaP incidence and outcomes.
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spelling pubmed-70462942020-03-09 Integrative comparison of the genomic and transcriptomic landscape between prostate cancer patients of predominantly African or European genetic ancestry Yuan, Jiao Kensler, Kevin H. Hu, Zhongyi Zhang, Youyou Zhang, Tianli Jiang, Junjie Xu, Mu Pan, Yutian Long, Meixiao Montone, Kathleen T. Tanyi, Janos L. Fan, Yi Zhang, Rugang Hu, Xiaowen Rebbeck, Timothy R. Zhang, Lin PLoS Genet Research Article Men of predominantly African Ancestry (AA) have higher prostate cancer (CaP) incidence and worse survival than men of predominantly European Ancestry (EA). While socioeconomic factors drive this disparity, genomic factors may also contribute to differences in the incidence and mortality rates. To compare the prevalence of prostate tumor genomic alterations and transcriptomic profiles by patient genetic ancestry, we evaluated genomic profiles from The Cancer Genome Atlas (TCGA) CaP cohort (n = 498). Patient global and local genetic ancestry were estimated by computational algorithms using genotyping data; 414 (83.1%) were EA, 61 (12.2%) were AA, 11 (2.2%) were East Asian Ancestry (EAA), 10 (2.0%) were Native American (NA), and 2 (0.4%) were other ancestry. Genetic ancestry was highly concordant with self-identified race/ethnicity. Subsequent analyses were limited to 61 AA and 414 EA cases. Significant differences were observed by ancestry in the frequency of SPOP mutations (20.3% AA vs. 10.0% EA; p = 5.6×10(−03)), TMPRSS2-ERG fusions (29.3% AA vs. 39.6% EA; p = 4.4×10(−02)), and PTEN deletions/losses (11.5% AA vs. 30.2% EA; p = 3.5×10(−03)). Differentially expressed genes (DEGs) between AAs and EAs showed significant enrichment for prostate eQTL target genes (p = 8.09×10(−48)). Enrichment of highly expressed DEGs for immune-related pathways was observed in AAs, and for PTEN/PI3K signaling in EAs. Nearly one-third of DEGs (31.3%) were long non-coding RNAs (DE-lncRNAs). The proportion of DE-lncRNAs with higher expression in AAs greatly exceeded that with lower expression in AAs (p = 1.2×10(−125)). Both ChIP-seq and RNA-seq data suggested a stronger regulatory role for AR signaling pathways in DE-lncRNAs vs. non-DE-lncRNAs. CaP-related oncogenic lncRNAs, such as PVT1, PCAT1 and PCAT10/CTBP1-AS, were found to be more highly expressed in AAs. We report substantial heterogeneity in the prostate tumor genome and transcriptome between EA and AA. These differences may be biological contributors to racial disparities in CaP incidence and outcomes. Public Library of Science 2020-02-14 /pmc/articles/PMC7046294/ /pubmed/32059012 http://dx.doi.org/10.1371/journal.pgen.1008641 Text en © 2020 Yuan et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Yuan, Jiao
Kensler, Kevin H.
Hu, Zhongyi
Zhang, Youyou
Zhang, Tianli
Jiang, Junjie
Xu, Mu
Pan, Yutian
Long, Meixiao
Montone, Kathleen T.
Tanyi, Janos L.
Fan, Yi
Zhang, Rugang
Hu, Xiaowen
Rebbeck, Timothy R.
Zhang, Lin
Integrative comparison of the genomic and transcriptomic landscape between prostate cancer patients of predominantly African or European genetic ancestry
title Integrative comparison of the genomic and transcriptomic landscape between prostate cancer patients of predominantly African or European genetic ancestry
title_full Integrative comparison of the genomic and transcriptomic landscape between prostate cancer patients of predominantly African or European genetic ancestry
title_fullStr Integrative comparison of the genomic and transcriptomic landscape between prostate cancer patients of predominantly African or European genetic ancestry
title_full_unstemmed Integrative comparison of the genomic and transcriptomic landscape between prostate cancer patients of predominantly African or European genetic ancestry
title_short Integrative comparison of the genomic and transcriptomic landscape between prostate cancer patients of predominantly African or European genetic ancestry
title_sort integrative comparison of the genomic and transcriptomic landscape between prostate cancer patients of predominantly african or european genetic ancestry
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046294/
https://www.ncbi.nlm.nih.gov/pubmed/32059012
http://dx.doi.org/10.1371/journal.pgen.1008641
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