Dissection of triple-negative breast cancer microenvironment and identification of potential therapeutic drugs using single-cell RNA sequencing analysis

Weilun Cheng; Wanqi Mi; Shiyuan Wang; Xinran Wang; Hui Jiang; Jing Chen; Kaiyue Yang; Wenqi Jiang; Jun Ye; Baoliang Guo; Yunpeng Zhang

doi:10.1016/j.jpha.2024.100975

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Weilun Cheng, Wanqi Mi, Shiyuan Wang, Xinran Wang, Hui Jiang, Jing Chen, Kaiyue Yang, Wenqi Jiang, Jun Ye, Baoliang Guo, Yunpeng Zhang. Dissection of triple-negative breast cancer microenvironment and identification of potential therapeutic drugs using single-cell RNA sequencing analysis[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2024.100975

Citation:

Weilun Cheng, Wanqi Mi, Shiyuan Wang, Xinran Wang, Hui Jiang, Jing Chen, Kaiyue Yang, Wenqi Jiang, Jun Ye, Baoliang Guo, Yunpeng Zhang. Dissection of triple-negative breast cancer microenvironment and identification of potential therapeutic drugs using single-cell RNA sequencing analysis[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2024.100975

Citation:

Weilun Cheng, Wanqi Mi, Shiyuan Wang, Xinran Wang, Hui Jiang, Jing Chen, Kaiyue Yang, Wenqi Jiang, Jun Ye, Baoliang Guo, Yunpeng Zhang. Dissection of triple-negative breast cancer microenvironment and identification of potential therapeutic drugs using single-cell RNA sequencing analysis[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2024.100975

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Dissection of triple-negative breast cancer microenvironment and identification of potential therapeutic drugs using single-cell RNA sequencing analysis

doi: 10.1016/j.jpha.2024.100975

a Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China;
b College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China;
c State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China

Funds:

This research was funded by the National Natural Science Foundation of China (Grant Nos: 62172131 and 81872135) and the Outstanding Youth Foundation of Heilongjiang Province of China (Grant No.: YQ2021C026).

Received Date: Feb. 02, 2024
Accepted Date: Mar. 30, 2024
Rev Recd Date: Mar. 28, 2024
Available Online: Apr. 10, 2024

Abstract

Abstract

Breast cancer remains a leading cause of mortality in women worldwide. Triplenegative breast cancer (TNBC) is a particularly aggressive subtype characterized by rapid progression, poor prognosis, and lack of clear therapeutic targets. In the clinic, delineation of tumor heterogeneity and development of effective drugs continue to pose considerable challenges. Within the scope of our study, high heterogeneity inherent to breast cancer was uncovered based on the landscape constructed from both tumor and healthy breast tissue samples. Notably, TNBC exhibited significant specificity regarding cell proliferation, differentiation, and disease progression. Significant associations between tumor grade, prognosis, and TNBC oncogenes were established via pseudotime trajectory analysis. Consequently, we further performed comprehensive characterization of the TNBC microenvironment. A crucial epithelial subcluster, E8, was identified as highly malignant and strongly associated with tumor cell proliferation in TNBC. Additionally, epithelial-mesenchymal transition-associated fibroblast and M2 macrophage subclusters exerted an influence on E8 through cellular interactions, contributing to tumor growth. Characteristic genes in these three cluster cells could therefore serve as potential therapeutic targets for TNBC. The collective findings provided valuable insights that assisted in the screening of a series of therapeutic drugs, such as pelitinib. We further confirmed the anti-cancer effect of pelitinib in an orthotopic 4T1 tumor-bearing mouse model. Overall, our study sheds light on the unique characteristics of TNBC at single-cell resolution and the crucial cell types associated with tumor cell proliferation that may serve as potent tools in the development of effective anti-cancer drugs.
- Triple-negative breast cancer,
- single-cell RNA sequencing,
- epithelialmesenchymal transition,
- macrophage polarization,
- therapeutic drugs,
- bioinformatics

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References

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