A unique transcriptomic landscape defines African-specific grade group 1 prostate cancer.

Background: Prostate cancer (PCa) exhibits significant ancestry-related disparity. While men of African ancestry experience higher overall mortality rates, this difference is most pronounced in Sub-Saharan Africa and for grade group 1 (GG1) disease, alluding to ancestry-specific biology. Despite this health disparity, African-relevant and prostate tumour GG1 inclusive data, specifically transcriptomic data, is lacking. In turn, this raises significant concerns with regards to adopting Eurocentric models to classify and manage assumed indolent disease for African men. The risk - suboptimal treatment decisions. Methods: Using a single technical and analytical pipeline, we generated total RNA sequencing data from fresh-frozen prostate tissue for 68 Black South African (40 GG1-PCa, 28 non-PCa) and 48 Australian European men (all GG1-PCa), performing ancestry-specific differential gene expression and pathway analysis. Sourcing public data enabled limited African American inclusive The Cancer Genome Atlas cross-validation (13 of 61 GG1-PCa), while Pan Prostate Cancer Group European ancestral data provided for deeper cross-ancestral comparative analyses (106 GG1-PCa, 17 non-PCa). Results: Identifying 5,652 differentially expressed genes between African and European ancestral GG1 tumours ( Conclusions: Revealing substantial transcriptomic divergence from European ancestral GG1 tumours, we identify African-specific transcriptomic features that may contribute to outcome disparities in this under-appreciated clinical group. Our study highlights not only a critical shortcoming in providing equitable PCa care for African men, but it also raises major concerns with regards to managing and treating African men using European-developed criteria.