Comprehensive signature analysis of drug metabolism differences in the White, Black and Asian prostate cancer patients
| Autor: | De-Ying Liao, Shan-Chao Zhao, Yang Liu, Jun-Hao Zhou, Cheng Yang, Ji-Ming Bao, Jia-Wei Zhou, Mingkun Chen, Qi-Zhao Zhou, Kang-Yi Xue, Zhi-Jian Liang, Ming Xia, Cun-Dong Liu, Hai-Feng Duan, Hong-Yi Wang, Wen-Bing Guo, Jian-Kun Yang, Xiao Xie, Zhi-Peng Huang |
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| Rok vydání: | 2020 |
| Předmět: |
Oncology
Drug Male Aging medicine.medical_specialty media_common.quotation_subject Single-nucleotide polymorphism Antineoplastic Agents Drug resistance Polymorphism Single Nucleotide White People Prostate cancer Epigenome Inhibitory Concentration 50 Asian People Internal medicine Cell Line Tumor medicine Ethnicity Humans RNA Messenger race media_common drug resistance CYP3A4 business.industry Prostatic Neoplasms Cell Biology Genomics comprehensive signature medicine.disease prostate cancer drug metabolism Black or African American Treatment Outcome ROC Curve Drug Resistance Neoplasm Area Under Curve GAS5 business Transcriptome Drug metabolism Metabolic Networks and Pathways Research Paper |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| Popis: | The drug response sensitivity and related prognosis of prostate cancer varied from races, while the original mechanism remains rarely understood. In this study, the comprehensive signature including transcriptomics, epigenome and single nucleotide polymorphisms (SNPs) of 485 PCa cases- including 415 Whites, 58 Blacks and 12 Asians from the TCGA database were analyzed to investigate the drug metabolism differences between races. We found that Blacks and Whites had a more prominent drug metabolism, cytotoxic therapy resistance, and endocrine therapy resistance than Asians, while Whites were more prominent in drug metabolism, cytotoxic therapy resistance and endocrine therapy resistance than Blacks. Subsequently, the targeted regulation analysis indicated that the racial differences in cytotoxic therapy resistance, endocrine therapy resistance, might originate from drug metabolisms, and 19 drug metabolism-related core genes were confirmed in the multi-omics network for subsequent analysis. Furthermore, we verified that CYP1A1, CYP3A4, CYP2B6, UGT2B17, UGT2B7, UGT1A8, UGT2B11, GAS5, SNHG6, XIST significantly affected antineoplastic drugs sensitivities in PCa cell lines, and these genes also showed good predictive efficiency of drug response and treatment outcomes for PCa in this cohort of patients. These findings revealed a comprehensive signature of drug metabolism differences for the Whites, Blacks and Asians, and it may provide some evidence for making individualized treatment strategies. |
| Databáze: | OpenAIRE |
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