Protein analysis of extracellular vesicles to monitor and predict therapeutic response in metastatic breast cancer

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.

Exosomes as a new frontier of cancer liquid biopsy

“…D Acoustic-based isolation / Thermophoretic enrichment. Copyright 2021 by Tayebi [ 67 ], 2019 by Liu [ 68 ], 2021 by Tian [ 69 ] …”

Extracellular Vesicles as Mediators of Therapy Resistance in the Breast Cancer Microenvironment

“…EV cargo consists of a number of bioactive molecules, including nucleic acids, lipids and membrane-bound and cytosolic proteins. The uptake of EVs is able to influence cell behaviour and as such, EVs are known to be important signalling particles, as well as diagnostic, predictive and prognostic biomarkers in diseases [ 39 ]. Although EVs can be categorised in a number of ways (e.g., based on size, cargo and biological role), they are most often classified based on their biogenesis, with exosomes and microvesicles being the most commonly discussed EV subtypes ( Figure 2 ).…”

“…This prospective cohort verified that a higher value of EV signature was significantly associated with an inferior PFS in Kaplan–Meier analysis (log-rank test: p = 0.033 for the EV). Collectively, these results imply that the EV signature may serve as an independent marker for metastatic BC prognosis [ 39 ].…”

Protein biomarkers in breast cancer-derived extracellular vesicles for use in liquid biopsies

“…The author suggested that analyzing individual EVs can provide more precise information for cancer diagnosis and that using a combination of proteins can improve the detection sensitivity (28). Then, Tian et al (46) found that the weighted sum of eight plasma EV protein markers [including mucin-1, CA-125, carcinoembryonic antigen, HER2, EGFR, prostate-specific membrane antigen (PSMA), EpCAM, and vascular endothelial growth factor (VEGF)] was able to distinguish among metastatic BC, nonmetastatic BC, and healthy donors with an overall accuracy of 91.1%. In addition, the aptasensor method used in this study has advantages in that preseparation of EVs is not needed, the total detection time is short (within 3 h), and it has a low cost (less than $1).…”