Abstract
Simple SummaryMen of African origin have a 2–3 times greater chance of developing prostate cancer than those of European origin, and of patients that are diagnosed with the disease, men of African descent are 2 times more likely to die compared to white men. Men of African origin are still greatly underrepresented in genetic studies and clinical trials. This, unfortunately, means that new discoveries in cancer treatment are missing key information on the group with a greater chance of mortality. The objective of this study was to increase our knowledge of prostate cancer in men undergoing a prostate biopsy. We carried out RNA sequencing of biopsy specimens and examined racial differences in prostate gene expression. A gene expression signature was uncovered which separated the men based on their race. Furthermore, within men of African descent this signature separated men with the most severe clinical characteristics.An emerging theory about racial differences in cancer risk and outcomes is that psychological and social stressors influence cellular stress responses; however, limited empirical data are available on racial differences in cellular stress responses among men who are at risk for adverse prostate cancer outcomes. In this study, we undertook a systems approach to examine molecular profiles and cellular stress responses in an important segment of African American (AA) and European American (EA) men: men undergoing prostate biopsy. We assessed the prostate transcriptome with a single biopsy core via high throughput RNA sequencing (RNA-Seq). Transcriptomic analyses uncovered impacted biological pathways including PI3K-Akt signaling pathway, Neuroactive ligand-receptor interaction pathway, and ECM-receptor interaction. Additionally, 187 genes mapping to the Gene Ontology (GO) terms RNA binding, structural constituent of ribosome, SRP-dependent co-translational protein targeting to membrane and the biological pathways, translation, L13a-mediated translational silencing of Ceruloplasmin expression were differentially expressed (DE) between EA and AA. This signature allowed separation of AA and EA patients, and AA patients with the most severe clinical characteristics. AA patients with elevated expression levels of this genomic signature presented with higher Gleason scores, a greater number of positive core biopsies, elevated dehydroepiandrosterone sulfate levels and serum vitamin D deficiency. Protein-protein interaction (PPI) network analysis revealed a high degree of connectivity between these 187 proteins.
Highlights
Stress occurs when a person cannot cope efficiently with the daily physical or psychological demands placed on the body [1,2,3,4]
An emerging hypothesis about cancer risk and outcomes in the context of racial disparities is that psychological and social stressors impact cellular stress responses [58,59]; limited empirical data are available on racial differences in cellular stress responses among men who are at risk for developing prostate cancer
When we examined the clinical characteristics of these extremal patients, we noted elevated Gleason scores, greater numbers of positive core biopsies, higher triglyceride levels, and lower CRP
Summary
Stress occurs when a person cannot cope efficiently with the daily physical or psychological demands placed on the body [1,2,3,4]. The primary hormonal stress mediators, catecholamines and glucocorticoids, elicit both beneficial and harmful effects. Allostatic load indicates disruption of biological processes in response to psychological and social stress. It is used as a marker of how much psychological and social stressors impact biological functioning [7,8,9]. Allostatic load values reflect chronic, steady state levels of stress as well as failure to terminate responses to acute stressors [10,11]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
