Thermophoretic glycan profiling of extracellular vesicles for triple-negative breast cancer management

Triple-negative breast cancer (TNBC) is a highly metastatic and heterogeneous type of breast cancer with poor outcomes. Precise, non-invasive methods for diagnosis, monitoring and prognosis of TNBC are particularly challenging due to a paucity of TNBC biomarkers. Glycans on extracellular vesicles (EVs) hold the promise as valuable biomarkers, but conventional methods for glycan analysis are not feasible in clinical practice. Here, we report that a lectin-based thermophoretic assay (EVLET) streamlines vibrating membrane filtration (VMF) and thermophoretic amplification, allowing for rapid, sensitive, selective and cost-effective EV glycan profiling in TNBC plasma. A pilot cohort study shows that the EV glycan signature reaches 91% accuracy for TNBC detection and 96% accuracy for longitudinal monitoring of TNBC therapeutic response. Moreover, we demonstrate the potential of EV glycan signature for predicting TNBC progression. Our EVLET system lays the foundation for non-invasive cancer management by EV glycans. Triple-negative breast cancer (TNBC) lacks precise diagnostic and monitoring methods due to limited biomarkers. Here the authors develop a lectin-based thermophoretic assay (EVLET) that combines vibrating membrane filtration and thermophoretic amplification for efficient extracellular vesicle (EV) glycan profiling in the plasma of TNBC patients, enabling non-invasive cancer management by leveraging EV glycans.