Open AccessMulti‐miRNA panel of tumor‐derived extracellular vesicles as promising diagnostic biomarkers of early‐stage breast cancer
Author(s) -
Kim Min Woo,
Park Sunyoung,
Lee Hyojung,
Gwak Hogyeong,
Hyun KyungA,
Kim Jee Ye,
Jung HyoIl,
Il Kim Seung
Publication year - 2021
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.15155
Subject(s) - breast cancer , microrna , biomarker , liquid biopsy , extracellular vesicles , stage (stratigraphy) , triple negative breast cancer , cancer , cancer biomarkers , extracellular vesicle , cancer research , medicine , oncology , receiver operating characteristic , microvesicles , biology , gene , genetics , microbiology and biotechnology , paleontology
Abstract 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.