miRNA panel from HER2+ and CD24+ plasma extracellular vesicle subpopulations as biomarkers of early-stage breast cancer

作者：Griffin B. Spychalski, Andrew A. Lin, Stephanie J. Yang, Hanfei Shen, J. Fernando del Rosario, Kyle Tien, Kate Rollert French, Miriyam Ghali, Stephanie S. Yee, Melinda Yin, Michael D. Feldman, Emily F. Conant, Susan P. Weinstein, Erica L. Carpenter, David Issadore, Anupma Nayak · 发表于：Breast Cancer Research · 年份：2025 · DOI：10.1186/s13058-025-02029-2 · 被引用次数：12 · 研究领域：Extracellular vesicles in disease、Biomarkers in Disease Mechanisms、Ferroptosis and cancer prognosis

BACKGROUND: Mammography screening has improved early breast cancer detection, leading to reduced mortality and lower rates of advanced breast cancer. However, mammography has a high false positive rate that results in over a million invasive breast biopsies of benign lesions in the US each year. Therefore, there is a need for noninvasive, blood-based diagnostics that can accurately assess risk of malignancy for women with indeterminate lesions identified by mammography, such as BI-RADS category 4 breast lesions. The aim of this study is to identify biomarkers from multiplexed extracellular vesicle liquid biopsy that can accurately classify mammographically detected BI-RADS 4 lesions. METHODS: We analyzed plasma from 113 prospectively enrolled subjects with BI-RADS 4 breast lesions, including 86 women with benign lesions and 27 women with malignant lesions (including 12 with stage I invasive carcinoma and 14 with ductal carcinoma in situ). None of the invasive carcinomas were metastatic. From each plasma sample, we used track etched magnetic nanopore technology to separately isolate HER2 and CD24 expressing extracellular vesicles (EVs) and measured their miRNA cargo using next-generation sequencing. We evaluated the performance of EV-miRNA biomarkers for classifying malignancy and applied LASSO classification to identify a panel of four complementary EV miRNA biomarkers that we validated by qPCR. RESULTS: We identified 19 differentially enriched miRNA from HER2+ EVs and 11 dif...