A Systems Approach to Interrogate Gene Expression Patterns in African American Men Presenting with Clinically Localized Prostate Cancer
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 canc...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-10-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/20/5143 |
| _version_ | 1797515058327060480 |
|---|---|
| author | Gary Hardiman Stephen J. Savage E. Starr Hazard Willian A. da Silveira Rebecca Morgan Adam Harris Melanie S. Jefferson Robert C. Wilson Susan Caulder Linda Ambrose Lewis Frey Bethany Wolf Sebastiano Gattoni-Celli Chanita Hughes Halbert |
| author_facet | Gary Hardiman Stephen J. Savage E. Starr Hazard Willian A. da Silveira Rebecca Morgan Adam Harris Melanie S. Jefferson Robert C. Wilson Susan Caulder Linda Ambrose Lewis Frey Bethany Wolf Sebastiano Gattoni-Celli Chanita Hughes Halbert |
| author_sort | Gary Hardiman |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T06:40:14Z |
| format | Article |
| id | doaj.art-2e99954f35734b90ae16a6a087738bdc |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T06:40:14Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-2e99954f35734b90ae16a6a087738bdc2023-11-22T17:40:57ZengMDPI AGCancers2072-66942021-10-011320514310.3390/cancers13205143A Systems Approach to Interrogate Gene Expression Patterns in African American Men Presenting with Clinically Localized Prostate CancerGary Hardiman0Stephen J. Savage1E. Starr Hazard2Willian A. da Silveira3Rebecca Morgan4Adam Harris5Melanie S. Jefferson6Robert C. Wilson7Susan Caulder8Linda Ambrose9Lewis Frey10Bethany Wolf11Sebastiano Gattoni-Celli12Chanita Hughes Halbert13Department of Medicine, Medical University of South Carolina (MUSC), Charleston, SC 29425, USADepartment of Urology, Medical University of South Carolina (MUSC), Charleston, SC 29425, USAAcademic Affairs Faculty, Medical University of South Carolina (MUSC), Charleston, SC 29425, USAFaculty of Medicine, Health and Life Sciences, School of Biological Sciences and Institute for Global Food Security, Queens University Belfast, Stranmillis Road, Belfast BT9 5AG, UKFaculty of Medicine, Health and Life Sciences, School of Biological Sciences and Institute for Global Food Security, Queens University Belfast, Stranmillis Road, Belfast BT9 5AG, UKFaculty of Medicine, Health and Life Sciences, School of Biological Sciences and Institute for Global Food Security, Queens University Belfast, Stranmillis Road, Belfast BT9 5AG, UKHollings Cancer Center, Medical University of South Carolina (MUSC), Charleston, SC 29425, USADepartment of Pathology and Laboratory Medicine, Medical University of South Carolina (MUSC), Charleston, SC 29425, USARalph H. Johnson VA Medical Center, Charleston, SC 29401, USARalph H. Johnson VA Medical Center, Charleston, SC 29401, USABiomedical Informatics Center (BMIC), Medical University of South Carolina (MUSC), Charleston, SC 29425, USADepartment of Public Health Sciences, Medical University of South Carolina (MUSC), Charleston, SC 29425, USARalph H. Johnson VA Medical Center, Charleston, SC 29401, USAHollings Cancer Center, Medical University of South Carolina (MUSC), Charleston, SC 29425, USAAn 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.https://www.mdpi.com/2072-6694/13/20/5143stressprecision medicineRNA-Seqprostatehealth disparitiesAfrican American |
| spellingShingle | Gary Hardiman Stephen J. Savage E. Starr Hazard Willian A. da Silveira Rebecca Morgan Adam Harris Melanie S. Jefferson Robert C. Wilson Susan Caulder Linda Ambrose Lewis Frey Bethany Wolf Sebastiano Gattoni-Celli Chanita Hughes Halbert A Systems Approach to Interrogate Gene Expression Patterns in African American Men Presenting with Clinically Localized Prostate Cancer Cancers stress precision medicine RNA-Seq prostate health disparities African American |
| title | A Systems Approach to Interrogate Gene Expression Patterns in African American Men Presenting with Clinically Localized Prostate Cancer |
| title_full | A Systems Approach to Interrogate Gene Expression Patterns in African American Men Presenting with Clinically Localized Prostate Cancer |
| title_fullStr | A Systems Approach to Interrogate Gene Expression Patterns in African American Men Presenting with Clinically Localized Prostate Cancer |
| title_full_unstemmed | A Systems Approach to Interrogate Gene Expression Patterns in African American Men Presenting with Clinically Localized Prostate Cancer |
| title_short | A Systems Approach to Interrogate Gene Expression Patterns in African American Men Presenting with Clinically Localized Prostate Cancer |
| title_sort | systems approach to interrogate gene expression patterns in african american men presenting with clinically localized prostate cancer |
| topic | stress precision medicine RNA-Seq prostate health disparities African American |
| url | https://www.mdpi.com/2072-6694/13/20/5143 |
| work_keys_str_mv | AT garyhardiman asystemsapproachtointerrogategeneexpressionpatternsinafricanamericanmenpresentingwithclinicallylocalizedprostatecancer AT stephenjsavage asystemsapproachtointerrogategeneexpressionpatternsinafricanamericanmenpresentingwithclinicallylocalizedprostatecancer AT estarrhazard asystemsapproachtointerrogategeneexpressionpatternsinafricanamericanmenpresentingwithclinicallylocalizedprostatecancer AT willianadasilveira asystemsapproachtointerrogategeneexpressionpatternsinafricanamericanmenpresentingwithclinicallylocalizedprostatecancer AT rebeccamorgan asystemsapproachtointerrogategeneexpressionpatternsinafricanamericanmenpresentingwithclinicallylocalizedprostatecancer AT adamharris asystemsapproachtointerrogategeneexpressionpatternsinafricanamericanmenpresentingwithclinicallylocalizedprostatecancer AT melaniesjefferson asystemsapproachtointerrogategeneexpressionpatternsinafricanamericanmenpresentingwithclinicallylocalizedprostatecancer AT robertcwilson asystemsapproachtointerrogategeneexpressionpatternsinafricanamericanmenpresentingwithclinicallylocalizedprostatecancer AT susancaulder asystemsapproachtointerrogategeneexpressionpatternsinafricanamericanmenpresentingwithclinicallylocalizedprostatecancer AT lindaambrose asystemsapproachtointerrogategeneexpressionpatternsinafricanamericanmenpresentingwithclinicallylocalizedprostatecancer AT lewisfrey asystemsapproachtointerrogategeneexpressionpatternsinafricanamericanmenpresentingwithclinicallylocalizedprostatecancer AT bethanywolf asystemsapproachtointerrogategeneexpressionpatternsinafricanamericanmenpresentingwithclinicallylocalizedprostatecancer AT sebastianogattonicelli asystemsapproachtointerrogategeneexpressionpatternsinafricanamericanmenpresentingwithclinicallylocalizedprostatecancer AT chanitahugheshalbert asystemsapproachtointerrogategeneexpressionpatternsinafricanamericanmenpresentingwithclinicallylocalizedprostatecancer AT garyhardiman systemsapproachtointerrogategeneexpressionpatternsinafricanamericanmenpresentingwithclinicallylocalizedprostatecancer AT stephenjsavage systemsapproachtointerrogategeneexpressionpatternsinafricanamericanmenpresentingwithclinicallylocalizedprostatecancer AT estarrhazard systemsapproachtointerrogategeneexpressionpatternsinafricanamericanmenpresentingwithclinicallylocalizedprostatecancer AT willianadasilveira systemsapproachtointerrogategeneexpressionpatternsinafricanamericanmenpresentingwithclinicallylocalizedprostatecancer AT rebeccamorgan systemsapproachtointerrogategeneexpressionpatternsinafricanamericanmenpresentingwithclinicallylocalizedprostatecancer AT adamharris systemsapproachtointerrogategeneexpressionpatternsinafricanamericanmenpresentingwithclinicallylocalizedprostatecancer AT melaniesjefferson systemsapproachtointerrogategeneexpressionpatternsinafricanamericanmenpresentingwithclinicallylocalizedprostatecancer AT robertcwilson systemsapproachtointerrogategeneexpressionpatternsinafricanamericanmenpresentingwithclinicallylocalizedprostatecancer AT susancaulder systemsapproachtointerrogategeneexpressionpatternsinafricanamericanmenpresentingwithclinicallylocalizedprostatecancer AT lindaambrose systemsapproachtointerrogategeneexpressionpatternsinafricanamericanmenpresentingwithclinicallylocalizedprostatecancer AT lewisfrey systemsapproachtointerrogategeneexpressionpatternsinafricanamericanmenpresentingwithclinicallylocalizedprostatecancer AT bethanywolf systemsapproachtointerrogategeneexpressionpatternsinafricanamericanmenpresentingwithclinicallylocalizedprostatecancer AT sebastianogattonicelli systemsapproachtointerrogategeneexpressionpatternsinafricanamericanmenpresentingwithclinicallylocalizedprostatecancer AT chanitahugheshalbert systemsapproachtointerrogategeneexpressionpatternsinafricanamericanmenpresentingwithclinicallylocalizedprostatecancer |