Association of self-identified race and genetic ancestry with the immunogenomic landscape of primary prostate cancer
The genomic and immune landscapes of prostate cancer differ by self-identified race. However, few studies have examined the genome-wide copy number landscape and immune content of matched cohorts with genetic ancestry data and clinical outcomes. Here, we assessed prostate cancer somatic copy number...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2023-02-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.162409 |
| _version_ | 1797634399849676800 |
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| author | Thiago Vidotto Eddie L. Imada Farzana Faisal Sanjana Murali Adrianna A. Mendes Harsimar Kaur Siqun Zheng Jianfeng Xu Edward M. Schaeffer William B. Isaacs Karen S. Sfanos Luigi Marchionni Tamara L. Lotan |
| author_facet | Thiago Vidotto Eddie L. Imada Farzana Faisal Sanjana Murali Adrianna A. Mendes Harsimar Kaur Siqun Zheng Jianfeng Xu Edward M. Schaeffer William B. Isaacs Karen S. Sfanos Luigi Marchionni Tamara L. Lotan |
| author_sort | Thiago Vidotto |
| collection | DOAJ |
| description | The genomic and immune landscapes of prostate cancer differ by self-identified race. However, few studies have examined the genome-wide copy number landscape and immune content of matched cohorts with genetic ancestry data and clinical outcomes. Here, we assessed prostate cancer somatic copy number alterations (sCNA) and tumor immune content of a grade-matched, surgically treated cohort of 145 self-identified Black (BL) and 145 self-identified White (WH) patients with genetic ancestry estimation. A generalized linear model adjusted with age, preoperative prostate-specific antigen (PSA), and Gleason Grade Group and filtered for germline copy number variations (gCNV) identified 143 loci where copy number varied significantly by percent African ancestry, clustering on chromosomes 6p, 10q, 11p, 12p, and 17p. Multivariable Cox regression models adjusted for age, preoperative PSA levels, and Gleason Grade Group revealed that chromosome 8q gains (including MYC) were significantly associated with biochemical recurrence and metastasis, independent of genetic ancestry. Finally, Treg density in BL and WH patients was significantly correlated with percent genome altered, and these findings were validated in the TCGA cohort. Taken together, our findings identify specific sCNA linked to genetic ancestry and outcome in primary prostate cancer and demonstrate that Treg infiltration varies by global sCNA burden in primary disease. |
| first_indexed | 2024-03-11T12:07:10Z |
| format | Article |
| id | doaj.art-ecd843645058485e9f5dc48d24f26852 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-03-11T12:07:10Z |
| publishDate | 2023-02-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-ecd843645058485e9f5dc48d24f268522023-11-07T16:25:10ZengAmerican Society for Clinical investigationJCI Insight2379-37082023-02-0183Association of self-identified race and genetic ancestry with the immunogenomic landscape of primary prostate cancerThiago VidottoEddie L. ImadaFarzana FaisalSanjana MuraliAdrianna A. MendesHarsimar KaurSiqun ZhengJianfeng XuEdward M. SchaefferWilliam B. IsaacsKaren S. SfanosLuigi MarchionniTamara L. LotanThe genomic and immune landscapes of prostate cancer differ by self-identified race. However, few studies have examined the genome-wide copy number landscape and immune content of matched cohorts with genetic ancestry data and clinical outcomes. Here, we assessed prostate cancer somatic copy number alterations (sCNA) and tumor immune content of a grade-matched, surgically treated cohort of 145 self-identified Black (BL) and 145 self-identified White (WH) patients with genetic ancestry estimation. A generalized linear model adjusted with age, preoperative prostate-specific antigen (PSA), and Gleason Grade Group and filtered for germline copy number variations (gCNV) identified 143 loci where copy number varied significantly by percent African ancestry, clustering on chromosomes 6p, 10q, 11p, 12p, and 17p. Multivariable Cox regression models adjusted for age, preoperative PSA levels, and Gleason Grade Group revealed that chromosome 8q gains (including MYC) were significantly associated with biochemical recurrence and metastasis, independent of genetic ancestry. Finally, Treg density in BL and WH patients was significantly correlated with percent genome altered, and these findings were validated in the TCGA cohort. Taken together, our findings identify specific sCNA linked to genetic ancestry and outcome in primary prostate cancer and demonstrate that Treg infiltration varies by global sCNA burden in primary disease.https://doi.org/10.1172/jci.insight.162409Genetics |
| spellingShingle | Thiago Vidotto Eddie L. Imada Farzana Faisal Sanjana Murali Adrianna A. Mendes Harsimar Kaur Siqun Zheng Jianfeng Xu Edward M. Schaeffer William B. Isaacs Karen S. Sfanos Luigi Marchionni Tamara L. Lotan Association of self-identified race and genetic ancestry with the immunogenomic landscape of primary prostate cancer JCI Insight Genetics |
| title | Association of self-identified race and genetic ancestry with the immunogenomic landscape of primary prostate cancer |
| title_full | Association of self-identified race and genetic ancestry with the immunogenomic landscape of primary prostate cancer |
| title_fullStr | Association of self-identified race and genetic ancestry with the immunogenomic landscape of primary prostate cancer |
| title_full_unstemmed | Association of self-identified race and genetic ancestry with the immunogenomic landscape of primary prostate cancer |
| title_short | Association of self-identified race and genetic ancestry with the immunogenomic landscape of primary prostate cancer |
| title_sort | association of self identified race and genetic ancestry with the immunogenomic landscape of primary prostate cancer |
| topic | Genetics |
| url | https://doi.org/10.1172/jci.insight.162409 |
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