Abstract LB346: Single-cell transcriptomic analysis of exosome-related genes in triple-negative breast cancer

Abstract Background: Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer with limited targeted therapeutic options. Exosomes, small membrane vesicles secreted by cells, play a crucial role in intercellular communication and material exchange. However, the role of exosome-related genes (ERGs) in TNBC remains unclear. Methods: We utilized single-cell RNA sequencing (scRNA-seq) from 10 TNBC samples and Weighted Gene Co-expression Network Analysis (WGCNA) to identify exosome-related genes and establish a prognostic model. The study’s methodology allows for an in-depth analysis of cellular heterogeneity within the tumor microenvironment and its impact on patient prognosis. Results: Our analysis identified 31,140 cells from TNBC samples, categorized into nine cell types, with epithelial cells exhibiting the highest exosome activity. A total of 232 differentially expressed genes (DEGs) related to exosome activity were identified, with 19 prognostic genes selected through univariate Cox regression, leading to the construction of an exosome-related gene signature (ERGS). Low ERGS scores correlated with poorer clinical outcomes, higher immune infiltrates, and immune-related pathways. Furthermore, we identified notable differences in biological functions and mutation profiles between the two ERGS groups. Additionally, the low ERGS score group exhibited lower tumor immune dysfunction and exclusion (TIDE) scores, immunophenoscore (IPS), and higher immune checkpoint expression, suggesting better immunotherapy outcomes. Conclusions: The findings indicate that the ERGS can effectively predict the prognosis and immunotherapy response of TNBC patients, highlighting its clinical relevance and potential as a biomarker for guiding treatment decisions. Citation Format: Yuan Zhang. Single-cell transcriptomic analysis of exosome-related genes in triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB346.