JCI Insight (Feb 2023)

Association of self-identified race and genetic ancestry with the immunogenomic landscape of primary prostate cancer

  • 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

Journal volume & issue
Vol. 8, no. 3

Abstract

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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.

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