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
- 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
Received: December 22, 2020 Accepted: May 13, 2021 Published: June 18, 2021
https://doi.org/10.18632/aging.203158How 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.
Abstract
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.
Abbreviations
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.