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May 17, 2026Journal of Extracellular Vesicles2 citationsOpen Access

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

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RURyosuke UekusaAYAkira Yokoi鵜鵜飼真由

Key Points

  • This research aims to assess the clinical relevance of DNA from extracellular vesicles (EVs) as biomarkers for high-grade serous ovarian carcinoma (HGSOC).
  • Evaluated CNV profiles of EV-DNA using droplet digital polymerase chain reaction.
  • Compared EV-DNA levels in malignant vs. benign ascites, along with tumor DNA concordance.
  • Identified predictive markers for response to PARP inhibitors through gene-based equations.
  • EV-DNA showed significantly higher levels in malignant ascites compared to benign cases (p < 0.05).
  • Strong predictive performance for olaparib response with AUC of 0.91 based on five specific genes.
  • Marked differences in CNV profiles between responders and nonresponders to PARP inhibitors.

Abstract

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.

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Cite This Study

Uekusa et al. (2026) studied this question.

synapsesocial.com/papers/6a095b3e7880e6d24efe0ecchttps://doi.org/10.1002/jev2.70308
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