1. Prostate tumors of native men from West Africa show biologically distinct pathways—A comparative genomic study
- Author
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Kosj Yamoah, Francis Adumata Asamoah, Timothy R. Rebbeck, Afua O. D Abrahams, Shivanshu Awasthi, Brandon A. Mahal, Joel Yarney, Sahar J Farahani, Mohamed F Jalloh, Jasreman Dhillon, James E. Mensah, Serigne Magueye Gueye, and Priti Lal
- Subjects
Male ,Oncology ,medicine.medical_specialty ,Urology ,medicine.medical_treatment ,Black People ,Biology ,Ghana ,White People ,Targeted therapy ,Prostate cancer ,Prostate ,Internal medicine ,medicine ,Carcinoma ,Humans ,PTEN ,Genetic Testing ,Biological Specimen Banks ,Comparative genomics ,Gene Expression Profiling ,Serine Endopeptidases ,Prostatic Neoplasms ,Cancer ,Genomics ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Ether-A-Go-Go Potassium Channels ,Senegal ,United States ,medicine.anatomical_structure ,biology.protein ,Signal Transduction - Abstract
BACKGROUND Native African men (NAM) experience a disproportionate burden of prostate cancer (PCa) and have higher mortality rates compared to European American men (EAM). While socioeconomic status has been implicated as a driver of this disparity, little is known about the genomic mechanisms and distinct biological pathways that are associated with PCa of native men of African origin. METHODS To understand biological factors that contribute to this disparity we utilized a total of 406 multi-institutional localized PCa samples, collected by Men of African Descent and Carcinoma of the Prostate biospecimen network and Moffitt Cancer Center/University of Pennsylvania Health science system. We performed comparative genomics and immunohistochemistry to identify the biomarkers that are highly enriched in NAM from west Africa and compared them with African American Men (AAM) and EAM. Quantified messenger RNA expression and Median H scores based on immune reactivity of staining cells, were compared using Mann Whitney test. For gene expression analysis, p values were further adjusted for multiple comparisons using false discovery rates. RESULTS Immunohistochemical analysis on selected biomarkers showed a consistent association between ETS related gene (ERG) status and race with 83% of NAM exhibiting tumors that lacked TMPRSS2-ERG translocation (ERGnegative ) as compared to AAM (71%) and EAM (52%). A higher proportion of NAM (29%) were also found to be double negative (ERGnegative and PTENLoss ) as compared to AAM (6%) and EAM (7%). NAM tumors had significantly higher immunoreactivity (H-score) for PSMA, and EZH2, whereas they have lower H-score for PTEN, MYC, AR, RB and Racemase, (all p
- Published
- 2021
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