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

doi:10.1111/cas.15155

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

Department of Mechanical Engineering

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

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.

Original language	English
Pages (from-to)	5078-5087
Number of pages	10
Journal	Cancer Science
Volume	112
Issue number	12
DOIs	https://doi.org/10.1111/cas.15155
Publication status	Published - 2021 Dec

Bibliographical note

Funding Information:
This research was supported by the Technology Innovation Program (20008829) funded by the Ministry of Trade, Industry and Energy. This work was supported by the National Research Foundation of Korea grant (2020M3A9I4039045, 2020R1A5A1018052, 2020R1I1A1A01067448, and 2021R1I1A1A01051594), and a Faculty Research Grant from the Yonsei University College of Medicine (6-2019-0067). The funders had no role in the study design, data collection, and analysis, the decision to publish, or the preparation of the manuscript. Professional editing assistance was provided by BioScience Writers, LLC.

Funding Information:
This research was supported by the Technology Innovation Program (20008829) funded by the Ministry of Trade, Industry and Energy. This work was supported by the National Research Foundation of Korea grant (2020M3A9I4039045, 2020R1A5A1018052, 2020R1I1A1A01067448, and 2021R1I1A1A01051594), and a Faculty Research Grant from the Yonsei University College of Medicine (6‐2019‐0067). The funders had no role in the study design, data collection, and analysis, the decision to publish, or the preparation of the manuscript. Professional editing assistance was provided by BioScience Writers, LLC.

Publisher Copyright:
© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/cas.15155

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

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.",

author = "Kim, {Min Woo} and Sunyoung Park and Hyojung Lee and Hogyeong Gwak and Hyun, {Kyung A.} and Kim, {Jee Ye} and Jung, {Hyo Il} and {Il Kim}, Seung",

note = "Funding Information: This research was supported by the Technology Innovation Program (20008829) funded by the Ministry of Trade, Industry and Energy. This work was supported by the National Research Foundation of Korea grant (2020M3A9I4039045, 2020R1A5A1018052, 2020R1I1A1A01067448, and 2021R1I1A1A01051594), and a Faculty Research Grant from the Yonsei University College of Medicine (6-2019-0067). The funders had no role in the study design, data collection, and analysis, the decision to publish, or the preparation of the manuscript. Professional editing assistance was provided by BioScience Writers, LLC. Funding Information: This research was supported by the Technology Innovation Program (20008829) funded by the Ministry of Trade, Industry and Energy. This work was supported by the National Research Foundation of Korea grant (2020M3A9I4039045, 2020R1A5A1018052, 2020R1I1A1A01067448, and 2021R1I1A1A01051594), and a Faculty Research Grant from the Yonsei University College of Medicine (6‐2019‐0067). The funders had no role in the study design, data collection, and analysis, the decision to publish, or the preparation of the manuscript. Professional editing assistance was provided by BioScience Writers, LLC. Publisher Copyright: {\textcopyright} 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.",

year = "2021",

month = dec,

doi = "10.1111/cas.15155",

language = "English",

volume = "112",

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AU - Kim, Min Woo

AU - Park, Sunyoung

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AU - Gwak, Hogyeong

AU - Hyun, Kyung A.

AU - Kim, Jee Ye

AU - Jung, Hyo Il

AU - Il Kim, Seung

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N2 - 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.

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

Abstract

Bibliographical note

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