Key Genomic Differences Identified in the Prostate Cancer of African American Men

The prostate tumors of African American men exhibit a unique immune repertoire and also have significant enrichment of proinflammatory immune pathways that are associated with poorer outcomes, according to a study published in Clinical Cancer Research.¹

According to researchers, these observed immuno-oncologic differences may aid in developing a genomically adaptive approach to treating prostate cancer in this patient population.

“Previous studies have looked at the immune landscape of prostate cancer in white or European American men but have lacked validation among their African American counterparts,” lead study author Kosj Yamoah, MD, PhD, assistant member of the Radiation Oncology and Cancer Epidemiology Programs at Moffitt Cancer Center, explained in a press release.² “Our genomic analysis, the largest of its kind, revealed there are major immune pathways that are significantly elevated in African American men, which can correlate with risk of cancer recurrence and poor outcomes.”

Using the Decipher GRID registry, investigators assessed a total of 1173 radiation-naïve radical prostatectomy samples with whole transcriptome data available. Transcriptomic expressions of 1260 immune-specific genes were then selected to evaluate immune-oncologic differences between the prostate tumors of African American and European American men.

The prostate tumors of African American men were found to have significant enrichment of major immune-oncologic pathways, including proinflammatory cytokines, IFNα, IFNγ, TNFα signaling, ILs, and epithelial–mesenchymal transition. These pathways can add to and increase the growth and spread of cancer cells.

Moreover, the tumor microenvironment of African American men was found to have a higher total immune content score (ICSHIGH) compared with 0 (37.8% vs. 21.9%, P = 0.003). Prostate tumors of African American men were also revealed to have lower DNA damage repair and were genomically radiosensitive as compared with European American men.

Overall, the immune biologic signatures observed suggest prostate cancer tumors in African American men may be more sensitive to radiotherapy and could have a better response to immunotherapy.

“Currently there are only 2 immunotherapy options for prostate cancer patients: the sipuleucel-T cell vaccine and pembrolizumab. However, not everyone responds to those therapies,” Yamoah noted. “Our study shows that African American men have higher overall immune content within their tumor microenvironment and higher expression of T lymphocytes. We can use that information to select a therapy that better targets their tumor and therefore improve their outcome.”

In addition, researchers also identified 6 genes with expression levels that were consistently different between African American and European American men. IFITM3 (IFN-inducible transmembrane protein 3) was one of the major proinflammatory genes overexpressed in African American men that predicted increased risk of biochemical recurrence selectively for African American men in both discovery (HRAAM = 2.30; 95% CI, 1.21-4.34; P = .01) and validation (HRAAM = 2.42; 95% CI, 1.52-3.86; P = .0001) but not in European American men. Of note, this gene also plays an important role in metastasis.

Moving forward, the investigators recommended that further study is still needed to determine if their findings can have positive implications on the treatment and management of prostate cancer in African American men.

References:

1. Awasthi S, Berglund A, Abraham-Miranda J, et al. Comparative Genomics Reveals Distinct Immune-oncologic Pathways in African American Men with Prostate Cancer. Clinical Cancer Research. doi: 10.1158/1078-0432.CCR-20-2925

2. Genomic Differences May Be Key to Overcoming Prostate Cancer Disparities Among African American Men [news release]. Tampa, Florida. Published October 21, 2020. Accessed November 23, 2020. https://www.newswise.com/articles/genomic-differences-may-be-key-to-overcoming-prostate-cancer-disparities-among-african-american-men?sc=sphr&xy=10021790