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

Abstract

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.

FASN Gene Methylation is Associated with Fatty Acid Synthase Expression and Clinical-genomic Features of Prostate Cancer

“… 16–20 ). We recently published Infinium EPIC methylation profiling data on a subset of this cohort ( 21 ) as described below, and samples were also arrayed on tissue microarray (TMA) for immunostaining studies as described previously ( 16 ). The second cohort was also from JHU but included in the Prostate Cancer Biorepository Network (PCBN cohort) and comprised 57 WH and 58 BL men with radical prostatectomies occurring between 2014 and 2016, also matched for Grade Group and selected to overrepresent higher Grade Groups, and arrayed on a TMA ( 22–26 ).…”

“…In addition, a subset of 111 of these patients had RNA microarray profiling which has been previously published on the Decipher platform ( 19 ). DNA samples isolated from formalin-fixed paraffin-embedded tumors were analyzed using the Infinium EPIC methylation array platform as described recently, and compared with 30 benign prostate tissues from a subset of the WH and BL men ( 21 ). The second cohort was the previously published The Cancer Genome Atlas (TCGA) prostatic adenocarcinoma cohort, where Infinium 450K methylation array profiling data were available from tumors from 502 men, with matched benign samples from 50 men ( 28 ).…”

“…Methylation pipelines were conducted according to our previously published study ( 21 ). Briefly, for JHU and NCI (GSE183019) cohorts, raw Infinium EPIC array methylation data were processed and normalized via SWAN (Subset quantile Within-Array Normalization) method using minfi in R. Individual beta values for CpGs were then obtained for all 850,000 methylation sites.…”

“…FASN methylation data are previously published and available in the GEO repository (GSE221219; ref. 21 ). For the JHU cohort, gene expression microarray data were previously published and available on GEO (GSE153352; ref.…”

The 29th Annual Prostate Cancer Foundation Scientific Retreat Report

“…Further research is necessary to fully understand the implications of these observed differences and their potential contribution to racial disparities in prostate cancer. Some of these data have recently been published 9 …”