A network-based integration for understanding racial disparity in prostate cancer
Compared to Caucasians (CAs), African Americans (AAs) have a higher rate of incidence and mortality in prostate cancer and are prone to be diagnosed at later stages. To understand this racial disparity, molecular features of different types, including gene expression, DNA methylation and other genom...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-03-01
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| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523321003181 |
| _version_ | 1818874245639307264 |
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| author | Baoyi Zhang Kevin Yao Chao Cheng |
| author_facet | Baoyi Zhang Kevin Yao Chao Cheng |
| author_sort | Baoyi Zhang |
| collection | DOAJ |
| description | Compared to Caucasians (CAs), African Americans (AAs) have a higher rate of incidence and mortality in prostate cancer and are prone to be diagnosed at later stages. To understand this racial disparity, molecular features of different types, including gene expression, DNA methylation and other genomic alterations, have been compared between tumor samples from the two races, but led to different disparity associated genes (DAGs). In this study, we applied a network-based algorithm to integrate a comprehensive set of genomic datasets and identified 130 core DAGs. Out of these genes, 78 were not identified by any individual dataset but prioritized and selected through network propagation. We found DAGs were highly enriched in several critical prostate cancer-related signaling transduction and cell cycle pathways and were more likely to be associated with patient prognosis in prostate cancer. Furthermore, DAGs were over-represented in prostate cancer risk genes identified from previous genome wide association studies. We also found DAGs were enriched in kinase and transcription factor encoding genes. Interestingly, for many of these prioritized kinases their association with racial disparity did not manifest from the original genomic/transcriptomic data but was reflected by their differential phosphorylation levels between AA and CA prostate tumor samples. Similarly, the disparity relevance of some transcription factors was not reflected at the mRNA or protein expression level, but at the activity level as demonstrated by their differential ability in regulating target gene expression. Our integrative analysis provided new candidate targets for improving prostate cancer treatment and addressing the racial disparity problem. |
| first_indexed | 2024-12-19T13:07:32Z |
| format | Article |
| id | doaj.art-6b299c2930b7409db395a2e5db679648 |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-12-19T13:07:32Z |
| publishDate | 2022-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-6b299c2930b7409db395a2e5db6796482022-12-21T20:20:01ZengElsevierTranslational Oncology1936-52332022-03-0117101327A network-based integration for understanding racial disparity in prostate cancerBaoyi Zhang0Kevin Yao1Chao Cheng2Department of Chemical and Biomolecular Engineering, Rice University, Houston, TX 77030, United StatesDepartment of Electrical and Computer Engineering, Texas A&M University, College Station, TX 77843, United StatesDepartment of Medicine, Baylor College of Medicine, Houston, TX 77030, United States; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, United States; Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX 77030, United States; Corresponding author at: Baylor College of Medicine, One Baylor Plaza, ICTR D100.1, Houston, TX 77030, United States.Compared to Caucasians (CAs), African Americans (AAs) have a higher rate of incidence and mortality in prostate cancer and are prone to be diagnosed at later stages. To understand this racial disparity, molecular features of different types, including gene expression, DNA methylation and other genomic alterations, have been compared between tumor samples from the two races, but led to different disparity associated genes (DAGs). In this study, we applied a network-based algorithm to integrate a comprehensive set of genomic datasets and identified 130 core DAGs. Out of these genes, 78 were not identified by any individual dataset but prioritized and selected through network propagation. We found DAGs were highly enriched in several critical prostate cancer-related signaling transduction and cell cycle pathways and were more likely to be associated with patient prognosis in prostate cancer. Furthermore, DAGs were over-represented in prostate cancer risk genes identified from previous genome wide association studies. We also found DAGs were enriched in kinase and transcription factor encoding genes. Interestingly, for many of these prioritized kinases their association with racial disparity did not manifest from the original genomic/transcriptomic data but was reflected by their differential phosphorylation levels between AA and CA prostate tumor samples. Similarly, the disparity relevance of some transcription factors was not reflected at the mRNA or protein expression level, but at the activity level as demonstrated by their differential ability in regulating target gene expression. Our integrative analysis provided new candidate targets for improving prostate cancer treatment and addressing the racial disparity problem.http://www.sciencedirect.com/science/article/pii/S1936523321003181Prostate cancerAfrican AmericanNetwork |
| spellingShingle | Baoyi Zhang Kevin Yao Chao Cheng A network-based integration for understanding racial disparity in prostate cancer Translational Oncology Prostate cancer African American Network |
| title | A network-based integration for understanding racial disparity in prostate cancer |
| title_full | A network-based integration for understanding racial disparity in prostate cancer |
| title_fullStr | A network-based integration for understanding racial disparity in prostate cancer |
| title_full_unstemmed | A network-based integration for understanding racial disparity in prostate cancer |
| title_short | A network-based integration for understanding racial disparity in prostate cancer |
| title_sort | network based integration for understanding racial disparity in prostate cancer |
| topic | Prostate cancer African American Network |
| url | http://www.sciencedirect.com/science/article/pii/S1936523321003181 |
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