학술논문
Prostate tumors of native men from West Africa show biologically distinct pathways-A comparative genomic study.
Document Type
Academic Journal
Author
Yamoah K; Department of Radiation Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.; Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.; Asamoah FA; National Center for Radiotherapy, Oncology and Nuclear Medicine, Korle Bu Teaching Hospital Accra, Accra, Ghana.; Abrahams AOD; Department of Pathology, University of Ghana Medical School, Korle bu Teaching Hospital, Accra, Ghana.; Awasthi S; Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.; Mensah JE; Department of Surgery, University of Ghana Medical School, Korle bu Teaching Hospital, Accra, Ghana.; Dhillon J; Department of Pathology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.; Mahal BA; Department of Radiation Oncology, University of Miami, Miami, Florida, USA.; Gueye SM; Hospital General Idrissa Pouye, Dakar, Senegal.; Jalloh M; Hospital General Idrissa Pouye, Dakar, Senegal.; Farahani SJ; Department of Pathology, Stony Brook University, New York city, New York, USA.; Lal P; Department of Pathology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.; Rebbeck TR; Dana Farber Cancer Institute and Harvard TH Chan School of Public Health, Boston, Massachusetts, USA.; Yarney J; National Center for Radiotherapy, Oncology and Nuclear Medicine, Korle Bu Teaching Hospital Accra, Accra, Ghana.
Source
Publisher: Wiley-Liss Country of Publication: United States NLM ID: 8101368 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-0045 (Electronic) Linking ISSN: 02704137 NLM ISO Abbreviation: Prostate Subsets: MEDLINE
Subject
Language
English
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 (ERG negative and PTEN Loss ) 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 < .05). Comparative genomics revealed that NAM had significant transcriptomic variability in AR-activity score. In pathways enrichment analysis NAM tumors exhibited the enrichment of proinflammatory pathways including cytokine, interleukins, inflammatory response, and nuclear factor kappa B signaling.
Conclusions: Prostate tumors in NAM are genomically distinct and are characterized by the dysregulation of several biomarkers. Furthermore, these tumors are also highly enriched for the major proinflammatory pathways. These distinct biological features may have implications for diagnosis and response to targeted therapy among Black men, globally.
(© 2021 Wiley Periodicals LLC.)
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 (ERG
Conclusions: Prostate tumors in NAM are genomically distinct and are characterized by the dysregulation of several biomarkers. Furthermore, these tumors are also highly enriched for the major proinflammatory pathways. These distinct biological features may have implications for diagnosis and response to targeted therapy among Black men, globally.
(© 2021 Wiley Periodicals LLC.)