DNA Copy Number Profiling in Extracellular Vesicles as Clinical Biomarkers of High-Grade Serous Ovarian Carcinoma

  • J Extracell Vesicles. 2026 May;15(5):e70308. doi: 10.1002/jev2.70308.
Ryosuke Uekusa  1 ,  Akira Yokoi  1  2  3 ,  Mayu Ukai  4 ,  Kosuke Yoshida  1  2 ,  Kunanon Chattrairat  5 ,  Takao Yasui  5 ,  Yasuhide Inokuma  6  7 ,  Masami Kitagawa  1 ,  Eri Asano-Inami  1 ,  Masato Yoshihara  1 ,  Satoshi Tamauchi  1 ,  Nobuhisa Yoshikawa  1 ,  Kaoru Niimi  1 ,  Juntaro Matsuzaki  8 ,  Takahiro Ochiya  9 ,  Anil K Sood  10  11 ,  Yusuke Yamamoto  12 ,  Hiroaki Kajiyama  1
Affiliations
  • 1. Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • 2. Nagoya University Institute For Advanced Research, Nagoya, Japan.
  • 3. Japan Science and Technology Agency (JST), Kawaguchi, Japan.
  • 4. Department of Gynecologic Oncology, Hyogo Cancer Center, Akashi, Hyogo, Japan.
  • 5. Department of Life Science and Technology, Institute of Science Tokyo, Yokohama, Japan.
  • 6. Division of Applied Chemistry, Faculty of Engineering, Hokkaido University, Sapporo, Hokkaido, Japan.
  • 7. Institute For Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Sapporo, Hokkaido, Japan.
  • 8. Division of Pharmacotherapeutics, Keio University Faculty of Pharmacy, Tokyo, Japan.
  • 9. Department of Molecular and Cellular Medicine, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.
  • 10. Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
  • 11. Center For RNA Interference and Non-Coding RNA, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
  • 12. Laboratory of Integrative Oncology, National Cancer Center Research Institute, Tokyo, Japan.
PMID: 42139280 DOI: 10.1002/jev2.70308
Abstract

Extracellular vesicles (EVs), including exosomes, circulate in body fluids and carry pathological genomic information. High-grade serous ovarian carcinoma (HGSOC) is the most common subtype of ovarian Cancer, characterized predominantly by copy number variations (CNVs). This study evaluated the clinical significance of EV-DNA focusing on CNV profiles and exploring its potential as a companion biomarker for predicting therapeutic response and supporting diagnosis in HGSOC. Droplet digital polymerase chain reaction detected concordant CNVs between tumor DNA and EV-DNA in ascites but not in serum. EV-DNA showed higher concordance with the CNV status of tumor DNA than cell-free DNA in ascites. The EV-DNA amount in malignant ascites was significantly higher than that in ascites from benign ovarian tumors (p < 0.05), and elevated EV-DNA was observed even in cytology-negative ovarian Cancer, suggesting an increase early in disease development. Moreover, CNV profiles showed marked differences between responders and nonresponders to poly(ADP-ribose) polymerase (PARP) inhibitors. An equation based on five genes (ARID1A, NOTCH3, CSMD3, ELP4, and BARD1) showed strong predictive performance for olaparib response (area under the curve = 0.91). Collectively, these findings indicate that the CNV status of EV-DNA may serve as a non-invasive companion biomarker for patient stratification and therapeutic monitoring in HGSOC.

Keywords
EV‐DNA; copy number variations; exosomes; extracellular vesicles; high‐grade serous ovarian carcinoma.
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