Comparative and integrative analysis of transcriptomic and epigenomic-wide DNA methylation changes in African American prostate cancer
African American (AA) men have the highest incidence and mortality rate from Prostate cancer (PCa) than any other racial/ethnic group. To date, PCa genomic studies have largely under-represented tumour samples from AA men. We measured genome-wide DNA methylation in benign and tumor prostate tissues...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Epigenetics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/15592294.2023.2180585 |
| _version_ | 1797678801999626240 |
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| author | Chad J. Creighton Flora Zhang Yiqun Zhang Patricia Castro Rong Hu Md Islam Somiranjan Ghosh Michael Ittmann Bernard Kwabi-Addo |
| author_facet | Chad J. Creighton Flora Zhang Yiqun Zhang Patricia Castro Rong Hu Md Islam Somiranjan Ghosh Michael Ittmann Bernard Kwabi-Addo |
| author_sort | Chad J. Creighton |
| collection | DOAJ |
| description | African American (AA) men have the highest incidence and mortality rate from Prostate cancer (PCa) than any other racial/ethnic group. To date, PCa genomic studies have largely under-represented tumour samples from AA men. We measured genome-wide DNA methylation in benign and tumor prostate tissues from AA men using the Illumina Infunium 850 K EPIC array. mRNA expression database from a subset of the AA biospecimen were used to assess correlation of transcriptome and methylation datasets. Genome-wide methylation analysis identified 11,460 probes that were significant (p < 0.01) and differentially methylated in AA PCa compared to normal prostate tissues and showed significant (p < 0.01) inverse-correlation with mRNA expression. Ingenuity pathway analysis and Gene Ontology analysis in our AA dataset compared with TCGA dataset showed similarities in methylation patterns: top candidate genes with significant hypermethylation and corresponding down-regulated gene expression were associated with biological pathways in hemidesmosome assembly, mammary gland development, epidermis development, hormone biosynthesis, and cell communication. In addition, top candidate genes with significant hypomethylation and corresponding up-regulated gene expression were associated with biological pathways in macrophage differentiation, cAMP-dependent protein kinase activity, protein destabilization, transcription co-repression, and fatty acid biosynthesis. In contrast, differences in genome-wide methylation in our AA dataset compared with TCGA dataset were enriched for genes in steroid signalling, immune signalling, chromatin structure remodelling and RNA processing. Overall, differential methylation of AMIGO3, IER3, UPB1, GRM7, TFAP2C, TOX2, PLSCR2, ZNF292, ESR2, MIXL1, BOLL, and FGF6 were significant and uniquely associated with PCa progression in our AA cohort. |
| first_indexed | 2024-03-11T23:05:13Z |
| format | Article |
| id | doaj.art-23d25d808dcd449d914fff78cc1dda88 |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-11T23:05:13Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-23d25d808dcd449d914fff78cc1dda882023-09-21T13:23:13ZengTaylor & Francis GroupEpigenetics1559-22941559-23082023-12-0118110.1080/15592294.2023.21805852180585Comparative and integrative analysis of transcriptomic and epigenomic-wide DNA methylation changes in African American prostate cancerChad J. Creighton0Flora Zhang1Yiqun Zhang2Patricia Castro3Rong Hu4Md Islam5Somiranjan Ghosh6Michael Ittmann7Bernard Kwabi-Addo8Baylor College of MedicineColgate UniversityBaylor College of MedicineMichael E. DeBakey Veterans Affairs Medical CenterGeorgetown UniversityGeorgetown UniversityHoward UniversityMichael E. DeBakey Veterans Affairs Medical CenterHoward UniversityAfrican American (AA) men have the highest incidence and mortality rate from Prostate cancer (PCa) than any other racial/ethnic group. To date, PCa genomic studies have largely under-represented tumour samples from AA men. We measured genome-wide DNA methylation in benign and tumor prostate tissues from AA men using the Illumina Infunium 850 K EPIC array. mRNA expression database from a subset of the AA biospecimen were used to assess correlation of transcriptome and methylation datasets. Genome-wide methylation analysis identified 11,460 probes that were significant (p < 0.01) and differentially methylated in AA PCa compared to normal prostate tissues and showed significant (p < 0.01) inverse-correlation with mRNA expression. Ingenuity pathway analysis and Gene Ontology analysis in our AA dataset compared with TCGA dataset showed similarities in methylation patterns: top candidate genes with significant hypermethylation and corresponding down-regulated gene expression were associated with biological pathways in hemidesmosome assembly, mammary gland development, epidermis development, hormone biosynthesis, and cell communication. In addition, top candidate genes with significant hypomethylation and corresponding up-regulated gene expression were associated with biological pathways in macrophage differentiation, cAMP-dependent protein kinase activity, protein destabilization, transcription co-repression, and fatty acid biosynthesis. In contrast, differences in genome-wide methylation in our AA dataset compared with TCGA dataset were enriched for genes in steroid signalling, immune signalling, chromatin structure remodelling and RNA processing. Overall, differential methylation of AMIGO3, IER3, UPB1, GRM7, TFAP2C, TOX2, PLSCR2, ZNF292, ESR2, MIXL1, BOLL, and FGF6 were significant and uniquely associated with PCa progression in our AA cohort.http://dx.doi.org/10.1080/15592294.2023.2180585clinically localized prostate cancerdna methylationgene expressiongenome-wide profilingcpg methylationafrican american men |
| spellingShingle | Chad J. Creighton Flora Zhang Yiqun Zhang Patricia Castro Rong Hu Md Islam Somiranjan Ghosh Michael Ittmann Bernard Kwabi-Addo Comparative and integrative analysis of transcriptomic and epigenomic-wide DNA methylation changes in African American prostate cancer Epigenetics clinically localized prostate cancer dna methylation gene expression genome-wide profiling cpg methylation african american men |
| title | Comparative and integrative analysis of transcriptomic and epigenomic-wide DNA methylation changes in African American prostate cancer |
| title_full | Comparative and integrative analysis of transcriptomic and epigenomic-wide DNA methylation changes in African American prostate cancer |
| title_fullStr | Comparative and integrative analysis of transcriptomic and epigenomic-wide DNA methylation changes in African American prostate cancer |
| title_full_unstemmed | Comparative and integrative analysis of transcriptomic and epigenomic-wide DNA methylation changes in African American prostate cancer |
| title_short | Comparative and integrative analysis of transcriptomic and epigenomic-wide DNA methylation changes in African American prostate cancer |
| title_sort | comparative and integrative analysis of transcriptomic and epigenomic wide dna methylation changes in african american prostate cancer |
| topic | clinically localized prostate cancer dna methylation gene expression genome-wide profiling cpg methylation african american men |
| url | http://dx.doi.org/10.1080/15592294.2023.2180585 |
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