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
• Publication Date: 2024-04-02T02:03:13Z
• Authors: Weilun Cheng; Wanqi Mi; Shiyuan Wang; Xinran Wang; Hui Jiang; Jing Chen; Kaiyue Yang; Wenqi Jiang; Jun Ye; Baoliang Guo; Yunpeng Zhang
• Keywords: Triple-negative breast cancer; Tumor progression

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