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

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.