Abstract

Molecular profiling of circulating extracellular vesicles (EVs) provides a promising noninvasive means to diagnose, monitor, and predict the course of metastatic breast cancer (MBC). However, the analysis of EV protein markers has been confounded by the presence of soluble protein counterparts in peripheral blood. Here we use a rapid, sensitive, and low-cost thermophoretic aptasensor (TAS) to profile cancer-associated protein profiles of plasma EVs without the interference of soluble proteins. We show that the EV signature (a weighted sum of eight EV protein markers) has a high accuracy (91.1 %) for discrimination of MBC, non-metastatic breast cancer (NMBC), and healthy donors (HD). For MBC patients undergoing therapies, the EV signature can accurately monitor the treatment response across the training, validation, and prospective cohorts, and serve as an independent prognostic factor for progression free survival in MBC patients. Together, this work highlights the potential clinical utility of EVs in management of MBC.

Highlights

  • Molecular profiling of circulating extracellular vesicles (EVs) provides a promising noninvasive means to diagnose, monitor, and predict the course of metastatic breast cancer (MBC)

  • Human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR) are ErbB family members, which are frequently overexpressed in BC and serve as therapeutic targets[34,35]

  • We demonstrate that EV protein markers measured by thermophoretic aptasensor (TAS) can be used to distinguish MBC from nonmetastatic breast cancer (NMBC) that may otherwise be indistinguishable using other circulating biomarkers such as plasma CA 15-3, CTCs, and ctDNA7,8,49,50

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Summary

Introduction

Molecular profiling of circulating extracellular vesicles (EVs) provides a promising noninvasive means to diagnose, monitor, and predict the course of metastatic breast cancer (MBC). Despite of the increasing availability of diagnosis and treatment, 25–28% of breast cancer (BC) patients are diagnosed as MBC with a 5-year survival rate of 27%2. MBC, real-time monitoring and prediction of therapy responses is critical to optimal personalized treatment regimens[3]. Tissue biopsy has been used for diagnosis of MBC, its invasiveness introduces risk and morbidity, and patients may not have adequate tissue available at the time of progression[4]. 15-3) is the most widely used plasma/serum biomarker in monitoring MBC, yet its response parallels disease response in only half of the patients[7,8]. The quantification and genetic characterization of circulating tumor cells (CTCs) and circulating tumor

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