Circulating Extracellular Vesicle Protein Biomarkers for the Early Detection of High-Grade Serous Ovarian Cancer

Small extracellular vesicles (sEVs), lipid-bilayer delimited particles (50-200 nm) released by cells, are emerging as a promising class of liquid biopsy biomarkers for elusive cancers such as high-grade serous ovarian cancer (HGSOC). HGSOC originates from the fallopian tube (FT), progressing from p53 signatures to a precursor lesion known as serous tubal intraepithelial carcinoma (STIC). We hypothesize that sEVs contribute to ovarian cancer pathogenesis, carry cargo reflective of their site of origin, and serve as diagnostic biomarkers for early detection. To test this, we established a case-control cohort using archival plasma samples from 30 HGSOC patients (10 early-stage and 20 late-stage) and 40 healthy controls (HC). sEVs were enriched by size exclusion chromatography and profiled by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Across all samples, 1,078 EV-associated proteins (exo-proteins) were identified, including 52 upregulated in early-stage HGSOC vs HC, and 59 upregulated in late-stage HGSOC vs healthy controls (HC) (log 2 FC>1, p-value