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Drug-resistant profiles of extracellular vesicles predict therapeutic response in TNBC patients receiving neoadjuvant chemotherapy

 Min Woo Kim  ;  Hyojung Lee  ;  Suji Lee  ;  Sol Moon  ;  Young Kim  ;  Joon Ye Kim  ;  Seung Il Kim  ;  Jee Ye Kim 
 BMC CANCER, Vol.24(1) : 185, 2024-02 
Journal Title
Issue Date
ATP Binding Cassette Transporter, Subfamily G, Member 2 / genetics ; Antineoplastic Combined Chemotherapy Protocols / therapeutic use ; Biomarkers, Tumor / metabolism ; Extracellular Vesicles* / metabolism ; Humans ; Neoadjuvant Therapy ; Neoplasm Proteins / metabolism ; Triple Negative Breast Neoplasms* / drug therapy ; Triple Negative Breast Neoplasms* / genetics ; Triple Negative Breast Neoplasms* / pathology
Extracellular vesicles ; Liquid biopsy ; Neoadjuvant chemotherapy ; Predictive biomarker ; TNBC
BackgroundPredicting tumor responses to neoadjuvant chemotherapy (NAC) is critical for evaluating prognosis and designing treatment strategies for patients with breast cancer; however, there are no reliable biomarkers that can effectively assess tumor responses. Therefore, we aimed to evaluate the clinical feasibility of using extracellular vesicles (EVs) to predict tumor response after NAC.MethodsDrug-resistant triple-negative breast cancer (TNBC) cell lines were successfully established, which developed specific morphologies and rapidly growing features. To detect resistance to chemotherapeutic drugs, EVs were isolated from cultured cells and plasma samples collected post-NAC from 36 patients with breast cancer.ResultsAmong the differentially expressed gene profiles between parental and drug-resistant cell lines, drug efflux transporters such as MDR1, MRP1, and BCRP were highly expressed in resistant cell lines. Drug efflux transporters have been identified not only in cell lines but also in EVs released from parental cells using immunoaffinity-based EV isolation. The expression of drug resistance markers in EVs was relatively high in patients with residual disease compared to those with a pathological complete response.ConclusionsThe optimal combination of drug-resistant EV markers was significantly efficient in predicting resistance to NAC with 81.82% sensitivity and 92.86% specificity.
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1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Min Woo(김민우)
Kim, Seung Il(김승일)
Kim, Jee Ye(김지예) ORCID logo https://orcid.org/0000-0003-3936-4410
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