Elevated levels of extracellular vesicles are associated with therapy failure and disease progression in breast cancer patients undergoing neoadjuvant chemotherapy

Abstract

Extracellular vesicles (EVs) have been discussed as a diagnostic tool for minimal residual disease (MRD) evaluation in breast cancer (BC) in addition to the analysis of circulating tumor cells (CTCs). Therefore, we investigated circulating EV levels as surrogate markers for disease monitoring and prediction of prognosis in primary, non-metastatic, locally advanced BC patients. EVs were enriched from blood samples of BC patients before and after neoadjuvant chemotherapy (NACT) and from healthy females. EV marker expression analysis was performed and EV sizes and concentrations were determined by nanoparticle tracking analysis. The results were associated with disease status, outcome and CTC presence, evaluated by gene expression analysis after enrichment. We demonstrated that i) the EV concentration was 40-fold higher in BC patients compared to healthy females, ii) the EV concentration increased during therapy, iii) an increased EV concentration pre-NACT was associated with therapy failure and iv) an elevated EV concentration post-NACT was associated with a reduced three-year progression-free and overall survival. Of note, residual stem cell-like and/or resistant CTCs after therapy were associated with a lower EV concentration post-NACT. Our study highlights that the concentration of EVs within BC blood samples may serve as a complementary parameter reflecting the status of MRD as well as therapy and disease outcome in parallel with CTC investigation.

Extracellular Vesicles in Cancer

“…These are described as secreted lipid bilayer-enclosed lumens and are claimed to be valuable reservoirs of liquid biopsy biomarker [156]. EVs (mainly EVs-associated proteins and microRNAs) are proved to be the biomarkers in breast cancer diagnosis [157,158].…”

Exosomal Transfer of MiR-500a-3p Confers Cisplatin Resistance and Stemness via Targeting FBXW7 in Gastric Cancer

“…In breast cancer, Kreger et al found that, compared to those untreated MDA-MB231 cells, the number of exosomes shed by the MDA-MB231 cells increased after paclitaxel treatment [31]. Besides in vitro model, paclitaxel was reported to induce a higher release of exosomes in 4T1-bearing mice and even in breast cancer patients, it was discovered that more exosomes were secreted after post-neoadjuvant chemotherapy as compared to the basal levels by NTA [32,33]. Similar to above mentioned references, our study showed that DDP resistant cells(MGC803/DDP and MKN45/DDP) could release more exosomes than their parental ones.…”

Extracellular Vesicles-Based Biomarkers Represent a Promising Liquid Biopsy in Endometrial Cancer

“…Of note, regarding the other precipitation-based strategies analyzed in our study, the main advantage of ExoGAG technology is the purity of the EVs obtained, which is a key factor for their posterior characterization. Linked to the extensive literature showing that EVs derived from tumor cell lines contribute to tumor invasion, chemoresistance, angiogenesis, tumor innervation, metastasis or immune escape [21,22], and to those evidences demonstrating that tumor-derived EVs are associated with advanced disease in different indications [23][24][25][26][27][28] and the response to therapy [29], the analysis of EV-based biomarkers should be expedited for the translation of this form of liquid biopsy into the clinics.…”