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Multi-miRNA panel of tumor-derived extracellular vesicles as promising diagnostic biomarkers of early-stage breast cancer

 Min Woo Kim  ;  Sunyoung Park  ;  Hyojung Lee  ;  Hogyeong Gwak  ;  Kyung-A Hyun  ;  Jee Ye Kim  ;  Hyo-Il Jung  ;  Seung Il Kim 
 CANCER SCIENCE, Vol.112(12) : 5078-5087, 2021-12 
Journal Title
Issue Date
Biomarkers, Tumor / genetics ; Breast Neoplasms / diagnosis* ; Breast Neoplasms / genetics ; Breast Neoplasms / pathology ; Case-Control Studies ; Cell Line, Tumor ; Databases, Genetic ; Early Detection of Cancer ; Epithelial Cell Adhesion Molecule / metabolism ; Extracellular Vesicles / genetics* ; Extracellular Vesicles / metabolism ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Integrin alpha6 / metabolism ; MCF-7 Cells ; MicroRNAs / genetics* ; Microfluidic Analytical Techniques / instrumentation ; Neoplasm Staging ; Up-Regulation*
biomarker ; early-stage breast cancer ; extracellular vesicles ; liquid biopsy ; microRNA
Extracellular vesicles (EV) have been emerging as potential biomarkers for disease monitoring. In particular, tumor-derived EV (TDE) are known to carry oncogenic miRNA, so they can be used for diagnosis of early cancer by analyzing the expression levels of EV-miRNA circulating in the blood. Here, using our novel microfluidic device, we rapidly and selectively isolate cancerous EV expressing breast cancer-derived surface markers CD49f and EpCAM within 2 minutes. Based on seven candidates of miRNA nominated from The Cancer Genome Atlas (TCGA) database, the expression levels of miRNA in TDE were validated in a total of 82 individuals, including 62 breast cancer patients and 20 healthy controls. Among seven candidates, four miRNAs (miR-9, miR-16, miR-21, and miR-429) from the EV were highly elevated in early-stage breast cancer patients compared with healthy donors. The combination of significant miRNAs from specific EV has high sensitivities of 0.90, 0.86, 0.88, and 0.84 of the area under the receiver operating characteristic curve (AUC) in each subtype (luminal A, luminal B, HER-2, and triple-negative) of early-stage breast cancer. Our results suggest that the combination of four miRNA signatures of specific EV could serve as a sensitive and specific biomarker and enable early diagnosis of breast cancer using liquid biopsy.
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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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