Pan-cancer single-cell landscape of drug-metabolizing enzyme genes.
Wei Mao, Tao Zhou, Feng Zhang, Maoxiang Qian, Jianqiang Xie, Zhengyan Li, Yang Shu, Yuan Li, Heng Xu
Author Information
Wei Mao: Department of Laboratory Medicine/Research Centre of Clinical Laboratory Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan.
Tao Zhou: Department of Laboratory Medicine/Research Centre of Clinical Laboratory Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan.
Feng Zhang: Center for Precision Medicine, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang.
Maoxiang Qian: Institute of Pediatrics and Department of Hematology and Oncology, National Children's Medical Center, Children's Hospital of Fudan University, Shanghai.
Jianqiang Xie: Department of Medicine and Surgery, Sichan Second Veterans Hospital.
Zhengyan Li: Department of Radiology, West China Hospital, Sichuan University.
Yang Shu: Gastric Cancer Center, West China Hospital, Sichuan University.
Yuan Li: Institute of Digestive Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Heng Xu: Department of Laboratory Medicine/Research Centre of Clinical Laboratory Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan.
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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