Pan-cancer single-cell landscape of drug-metabolizing enzyme genes.

IF 1.7 3区医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Pharmacogenetics and genomics Pub Date : 2024-09-01 Epub Date: 2024-05-17 DOI:10.1097/FPC.0000000000000538

Wei Mao, Tao Zhou, Feng Zhang, Maoxiang Qian, Jianqiang Xie, Zhengyan Li, Yang Shu, Yuan Li, Heng Xu

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引用次数: 0

Abstract

Objective: Varied expression of drug-metabolizing enzymes (DME) genes dictates the intensity and duration of drug response in cancer treatment. This study aimed to investigate the transcriptional profile of DMEs in tumor microenvironment (TME) at single-cell level and their impact on individual responses to anticancer therapy.

Methods: Over 1.3 million cells from 481 normal/tumor samples across 9 solid cancer types were integrated to profile changes in the expression of DME genes. A ridge regression model based on the PRISM database was constructed to predict the influence of DME gene expression on drug sensitivity.

Results: Distinct expression patterns of DME genes were revealed at single-cell resolution across different cancer types. Several DME genes were highly enriched in epithelial cells (e.g. GPX2, TST and CYP3A5 ) or different TME components (e.g. CYP4F3 in monocytes). Particularly, GPX2 and TST were differentially expressed in epithelial cells from tumor samples compared to those from normal samples. Utilizing the PRISM database, we found that elevated expression of GPX2, CYP3A5 and reduced expression of TST was linked to enhanced sensitivity of particular chemo-drugs (e.g. gemcitabine, daunorubicin, dasatinib, vincristine, paclitaxel and oxaliplatin).

Conclusion: Our findings underscore the varied expression pattern of DME genes in cancer cells and TME components, highlighting their potential as biomarkers for selecting appropriate chemotherapy agents.

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泛癌症单细胞药物代谢酶基因图谱。

目的：药物代谢酶（DME）基因的不同表达决定了癌症治疗中药物反应的强度和持续时间。本研究旨在从单细胞水平研究肿瘤微环境（TME）中药物代谢酶的转录谱及其对抗癌治疗个体反应的影响：方法：研究人员整合了来自9种实体瘤类型的481个正常/肿瘤样本的130多万个细胞，以分析DME基因表达的变化。基于 PRISM 数据库构建了脊回归模型，以预测 DME 基因表达对药物敏感性的影响：结果：在不同癌症类型中，DME基因在单细胞分辨率下的表达模式各不相同。一些DME基因在上皮细胞（如GPX2、TST和CYP3A5）或不同的TME成分（如单核细胞中的CYP4F3）中高度富集。与正常样本相比，GPX2 和 TST 在肿瘤样本上皮细胞中的表达尤其不同。利用 PRISM 数据库，我们发现 GPX2、CYP3A5 表达的升高和 TST 表达的降低与特定化疗药物（如吉西他滨、达诺比星、达沙替尼、长春新碱、紫杉醇和奥沙利铂）敏感性的增强有关：我们的研究结果强调了DME基因在癌细胞和TME成分中的不同表达模式，凸显了它们作为生物标记物选择适当化疗药物的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmacogenetics and genomics 医学-生物工程与应用微生物

CiteScore

3.20

自引率

3.80%

发文量

审稿时长

3 months

期刊介绍： Pharmacogenetics and Genomics is devoted to the rapid publication of research papers, brief review articles and short communications on genetic determinants in response to drugs and other chemicals in humans and animals. The Journal brings together papers from the entire spectrum of biomedical research and science, including biochemistry, bioinformatics, clinical pharmacology, clinical pharmacy, epidemiology, genetics, genomics, molecular biology, pharmacology, pharmaceutical sciences, and toxicology. Under a single cover, the Journal provides a forum for all aspects of the genetics and genomics of host response to exogenous chemicals: from the gene to the clinic.