Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Nagoya University Institute for Advanced Research, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan.
Sci Adv. 2023 Jul 7;9(27):eade6958. doi: 10.1126/sciadv.ade6958.
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.
癌细胞衍生的细胞外囊泡 (EVs) 具有独特的蛋白质谱，因此有望成为疾病生物标志物的候选物。高级别浆液性卵巢癌 (HGSOC) 是上皮性卵巢癌的致命亚型，我们旨在鉴定 HGSOC 特异性的膜蛋白。通过 LC-MS/MS 分析细胞系或患者血清和腹水来源的小细胞外囊泡 (sEVs) 和中/大细胞外囊泡 (m/lEVs)，揭示了这两种 EV 亚型具有独特的蛋白质组学特征。多步验证步骤鉴定了 FRα、Claudin-3 和 TACSTD2 为 HGSOC 特异性 sEV 蛋白，但未鉴定出与 m/lEV 相关的候选物。此外，为了使用简单易用的微流控装置进行 EV 分离，开发了聚酮涂层纳米线 (pNW)，其可从生物流体中有效纯化 sEVs。通过 pNW 分离的 sEV 的多重阵列分析在癌症患者中显示出特异性检测能力，并预测了临床状态。总之，pNW 对 HGSOC 特异性标志物的检测作为临床生物标志物具有广阔的应用前景，这些研究结果为 HGSOC 患者中不同 EV 的详细蛋白质组学方面提供了依据。
