Identifying high-grade serous ovarian carcinoma-specific extracellular vesicles by polyketone-coated nanowires

Akira Yokoi; Mayu Ukai; Takao Yasui; Yasuhide Inokuma; Kim Hyeon-Deuk; Juntaro Matsuzaki; Kosuke Yoshida; Masami Kitagawa; Kunanon Chattrairat; Mikiko Iida; Taisuke Shimada; Yumehiro Manabe; I-Ya Chang; Eri Asano-Inami; Yoshihiro Koya; Akihiro Nawa; Kae Nakamura; Tohru Kiyono; Tomoyasu Kato; Akihiko Hirakawa; Yusuke Yoshioka; Takahiro Ochiya; Takeshi Hasegawa; Yoshinobu Baba; Yusuke Yamamoto; Hiroaki Kajiyama

doi:10.1126/sciadv.ade6958

Identifying high-grade serous ovarian carcinoma-specific extracellular vesicles by polyketone-coated nanowires

Sci Adv. 2023 Jul 7;9(27):eade6958. doi: 10.1126/sciadv.ade6958. Epub 2023 Jul 7.

Authors

Akira Yokoi^{1

2

3}, Mayu Ukai¹, Takao Yasui^{4

5

6

7}, Yasuhide Inokuma^{3

6

8

9}, Kim Hyeon-Deuk^{6

10}, Juntaro Matsuzaki¹¹, Kosuke Yoshida^{1

2}, Masami Kitagawa^{1

12}, Kunanon Chattrairat⁵, Mikiko Iida⁵, Taisuke Shimada⁵, Yumehiro Manabe⁸, I-Ya Chang¹⁰, Eri Asano-Inami^{1

12}, Yoshihiro Koya^{1

12}, Akihiro Nawa^{1

12}, Kae Nakamura^{1

13}, Tohru Kiyono¹⁴, Tomoyasu Kato¹⁵, Akihiko Hirakawa¹⁶, Yusuke Yoshioka¹⁷, Takahiro Ochiya¹⁷, Takeshi Hasegawa¹⁸, Yoshinobu Baba^{5

7

19}, Yusuke Yamamoto²⁰, Hiroaki Kajiyama¹¹

Affiliations

¹ Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
² Nagoya University Institute for Advanced Research, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan.
³ Japan Science and Technology Agency (JST), FOREST, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
⁴ Department of Life Science and Technology, Tokyo Institute of Technology, Nagatsuta 4259, Midori-ku, Yokohama 226-8501, Japan.
⁵ Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan.
⁶ Japan Science and Technology Agency (JST), PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
⁷ Institute of Nano-Life-Systems, Institutes of Innovation for Future Society, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan.
⁸ Division of Applied Chemistry, Faculty of Engineering, Hokkaido University, Kita 13 Nishi 8 Kita-ku, Sapporo, Hokkaido 060-8628, Japan.
⁹ Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Kita 21, Nishi 10, Kita-ku, Sapporo, Hokkaido 001-0021, Japan.
¹⁰ Department of Chemistry, Kyoto University, Yoshida-honmachi, Sakyo-ku, Kyoto 606-8502, Japan.
¹¹ Division of Pharmacotherapeutics, Keio University Faculty of Pharmacy, 2-15-45 Mita, Minato-ku, Tokyo 108-8345, Japan.
¹² Bell Research Center, Department of Obstetrics and Gynecology Collaborative Research, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
¹³ Center for Low-Temperature Plasma Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan.
¹⁴ Project for Prevention of HPV-related Cancer, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
¹⁵ Department of Gynecologic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
¹⁶ Department of Clinical Biostatistics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
¹⁷ Department of Molecular and Cellular Medicine, Institute of Medical Science, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.
¹⁸ Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan.
¹⁹ Institute of Quantum Life Science, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Kanagawa, Inage-ku, Chiba, Chiba 263-8555, Japan.
²⁰ Laboratory of Integrative Oncology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.

Abstract

Cancer cell-derived extracellular vesicles (EVs) have unique protein profiles, making them promising targets as disease biomarkers. High-grade serous ovarian carcinoma (HGSOC) is the deadly subtype of epithelial ovarian cancer, and we aimed to identify HGSOC-specific membrane proteins. Small EVs (sEVs) and medium/large EVs (m/lEVs) from cell lines or patient serum and ascites were analyzed by LC-MS/MS, revealing that both EV subtypes had unique proteomic characteristics. Multivalidation steps identified FRα, Claudin-3, and TACSTD2 as HGSOC-specific sEV proteins, but m/lEV-associated candidates were not identified. In addition, for using a simple-to-use microfluidic device for EV isolation, polyketone-coated nanowires (pNWs) were developed, which efficiently purify sEVs from biofluids. Multiplexed array assays of sEVs isolated by pNW showed specific detectability in cancer patients and predicted clinical status. In summary, the HGSOC-specific marker detection by pNW are a promising platform as clinical biomarkers, and these insights provide detailed proteomic aspects of diverse EVs in HGSOC patients.

MeSH terms

Biomarkers
Chromatography, Liquid
Extracellular Vesicles* / metabolism
Female
Humans
Nanowires*
Ovarian Neoplasms* / metabolism
Proteins
Proteomics
Tandem Mass Spectrometry

Substances

Biomarkers
Proteins