Abstract
Background: Breast cancer represents a significant contributor to cancer-related mortality among women worldwide, with triple-negative breast cancer (TNBC) often exhibiting more aggressive clinical features and a heightened lethality rate. The emergence of malignant progression, along with issues of drug resistance, poses substantial challenges in the clinical management of this disease. Methods: The analysis of gene expression profiles at the single-cell level was conducted on circulating tumor cells (CTCs) obtained from TNBC patients, with the objective of identifying specific marker genes associated with CTCs. The TCGA database served as the training cohort for the development of a prognostic CTCs signature model, while the METABRIC dataset was utilized as the validation cohort to assess the robustness of the CTCs signature model. Furthermore, we investigated the differences in prognosis, immune scores, tumor mutational burden, and responses to immunotherapy and chemotherapy across various risk groups established based on the CTCs signature model. Colony formation and transwell assays were conducted to assess the influence of CTCs signature genes on cellular proliferation and invasive capabilities. Results: Seven marker genes associated with CTCs (BLOC1S3, FOXD2, GZMB, KCNJ13, NTRK3, SOAT2, and ZNF589) were identified and incorporated into a CTCs signature model. The risk score derived from this model stratified TNBC patients into high-risk and low-risk groups. Notably, the overall survival (OS) rate for the low-risk group was significantly higher than that of the high-risk group. Furthermore, the low-risk cohort exhibited more favorable prognostic outcomes and demonstrated heightened sensitivity to both immunotherapy and chemotherapy. Finally, knockdown experiments conducted in TNBC cell lines demonstrated that CTCs signature genes play a crucial role in the regulation of cellular proliferation and invasion. Conclusion: The CTCs signature model offers novel insights into the prognostic significance of CTC marker genes in TNBC. This understanding may serve as a valuable reference for predicting responses to immunotherapy and chemotherapy, as well as for revealing the molecular mechanisms and therapeutic targets of TNBC.