A network-based integration for understanding racial disparity in prostate cancer
| العنوان: | A network-based integration for understanding racial disparity in prostate cancer |
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| المؤلفون: | Baoyi Zhang, Kevin Yao, Chao Cheng |
| المصدر: | Translational Oncology, Vol 17, Iss, Pp 101327-(2022) Translational Oncology |
| بيانات النشر: | Elsevier, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | RPPA, reverse phase protein array, Cancer Research, Prostate cancer, CNV, copy number variation, FDR, false discovery rate, GEO, gene expression omnibus, CRPC, castration-resistant prostate cancer, education, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Network, CA, Caucasian, body regions, PRAD, prostate adenocarcinoma, fluids and secretions, Oncology, parasitic diseases, GO, Gene Ontology, GWAS, genome-wide association study, African American, AA, African American, DAG, racial disparity associated gene, RC254-282, Original Research |
| الوصف: | Highlights • Integrative analysis identified 130 core racial disparity associated genes. • The racial disparity associated genes were enriched for prostate cancer risk genes. • The racial disparity genes were more likely to be prognostic. • Kinases show differential phosphorylation levels between different races. • Transcription factors show differential regulatory activities between different races. 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. |
| اللغة: | English |
| تدمد: | 1936-5233 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::911176fe31b6ce95894e7f78f892bc18 http://www.sciencedirect.com/science/article/pii/S1936523321003181 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....911176fe31b6ce95894e7f78f892bc18 |
| قاعدة البيانات: | OpenAIRE |
Full Text via ClinicalKey | تدمد: | 19365233 |
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