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A unique transcriptomic landscape defines African-specific grade group 1 prostate cancer
Eva Ferlev Jensby1, Korawich Uthayopas2, Md Mehedi Hasan2
1Aarhus University Hospital.
Research Square
|May 4, 2026
Summary
Prostate cancer (PCa) transcriptomic data reveals significant ancestry-specific differences between African and European men. These findings highlight the need for tailored diagnostic and treatment strategies to address health disparities in PCa care.
Area of Science:
- Genomics
- Oncology
- Population Health
Background:
- Prostate cancer (PCa) disproportionately affects men of African ancestry, with higher mortality rates, particularly for grade group 1 (GG1) disease.
- Existing research lacks African-relevant transcriptomic data for GG1 PCa, raising concerns about applying Eurocentric models to African populations.
- This data gap risks suboptimal treatment decisions and management strategies for African men with PCa.
Purpose of the Study:
- To investigate ancestry-specific transcriptomic differences in prostate cancer, focusing on GG1 disease.
- To compare gene expression and pathway analysis between Black South African and Australian European men with PCa.
- To identify potential molecular drivers of health disparities in prostate cancer outcomes.
Main Methods:
- Generated total RNA sequencing data from fresh-frozen prostate tissues of Black South African (n=68) and Australian European (n=48) men.
- Performed ancestry-specific differential gene expression and pathway analysis.
- Utilized public data for cross-validation with African American and European ancestral cohorts.
Main Results:
- Identified 5,652 differentially expressed genes between African and European ancestral GG1 tumors, with key tumor suppressor genes downregulated in African tumors.
- Observed significant African-specific negative enrichment in six metabolic and six immune-related pathways.
- Found lower immune, stromal, and angiogenesis scores in African versus European GG1 tumors, with African tissues showing increased differential gene expression in PSA-high vs. PSA-low tissues.
Conclusions:
- Substantial transcriptomic divergence exists between African and European ancestral GG1 tumors, indicating African-specific molecular features.
- These findings underscore a critical gap in equitable PCa care for African men and raise concerns about using European-derived criteria for their management.
- The study highlights the urgent need for research and clinical guidelines that account for ancestry-specific biology in prostate cancer.
