Research Paper Volume 13, Issue 12 pp 16316—16340

Comprehensive signature analysis of drug metabolism differences in the White, Black and Asian prostate cancer patients

Yang Liu1, *, , Jia-Wei Zhou1, *, , Cun-Dong Liu1, *, , Jian-Kun Yang1, , De-Ying Liao1, , Zhi-Jian Liang1, , Xiao Xie1, , Qi-Zhao Zhou1, , Kang-Yi Xue1, , Wen-Bing Guo1, , Ming Xia1, , Jun-Hao Zhou1, , Ji-Ming Bao1, , Cheng Yang1, , Hai-Feng Duan1, , Hong-Yi Wang1, , Zhi-Peng Huang1, , Shan-Chao Zhao1,2, , Ming-Kun Chen1,2, ,

  • 1 Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China
  • 2 Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
* Equal contribution

Received: December 22, 2020       Accepted: May 13, 2021       Published: June 18, 2021
How to Cite

Copyright: © 2021 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.


M: methylation; MUT: mutations; SNP: single nucleotide polymorphism; DMP: drug metabolism pathways; IC50: half-maximal inhibitory concentration; EC50: half-maximal effect concentration; AUC: area under curve; AUCs: area under the dose-response curve; ROC: receiver operating characteristic curve; SD: standard deviation; PCa: prostate cancer; OS: overall survival; CSS: cancer specific survival; Black: Black or Black American.