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腹水高 EpCAM 阳性细胞外囊泡浓度与晚期高级别浆液性卵巢癌患者无进展生存期缩短相关。

Higher EpCAM-Positive Extracellular Vesicle Concentration in Ascites Is Associated with Shorter Progression-Free Survival of Patients with Advanced High-Grade Serous Carcinoma.

机构信息

Division of Gynecology and Obstetrics, University Medical Centre Ljubljana, SI-1000 Ljubljana, Slovenia.

Department of Gynecology and Obstetrics, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia.

出版信息

Int J Mol Sci. 2024 Jun 20;25(12):6780. doi: 10.3390/ijms25126780.

Abstract

Platinum-resistant high-grade serous carcinoma (HGSC) is an incurable disease, so biomarkers that could help with timely treatment adjustments and personalized approach are extensively being sought. Tumor-derived extracellular vesicles (EVs) that can be isolated from ascites and blood of HGSC patients are such promising biomarkers. Epithelial cell adhesion molecule (EpCAM) expression is upregulated in most epithelium-derived tumors; however, studies on prognostic value of EpCAM overexpression in ovarian carcinoma have shown contradictory results. The aim of our study was to evaluate the potential of total and EpCAM-positive EVs as prognostic and predictive biomarkers for advanced HGSC. Flow cytometry was used to determine the concentration of total and EpCAM-positive EVs in paired pretreatment ascites and plasma samples of 37 patients with advanced HGSC who underwent different first-line therapy. We found that higher EpCAM-positive EVs concentration in ascites is associated with shorter progression-free survival (PFS) regardless of treatment strategy. We also found a strong correlation of EpCAM-positive EVs concentration between ascites and plasma. Our findings indicate that EpCAM-positive EVs in ascites of patients with advanced HGSC have the potential to serve as prognostic biomarkers for predicting early recurrence and thereby likelihood of more aggressive tumor biology and development of chemoresistance.

摘要

铂耐药高级别浆液性卵巢癌(HGSC)是一种不可治愈的疾病,因此广泛寻求能够帮助及时调整治疗和个性化治疗的生物标志物。可以从 HGSC 患者的腹水和血液中分离出肿瘤来源的细胞外囊泡(EVs),这些囊泡是很有前途的生物标志物。上皮细胞黏附分子(EpCAM)在大多数上皮来源的肿瘤中表达上调;然而,关于 EpCAM 过表达在卵巢癌中的预后价值的研究结果却相互矛盾。我们的研究旨在评估总 EVs 和 EpCAM 阳性 EVs 作为晚期 HGSC 患者预后和预测生物标志物的潜力。我们使用流式细胞术来确定 37 名接受不同一线治疗的晚期 HGSC 患者预处理时腹水和血浆配对样本中总 EVs 和 EpCAM 阳性 EVs 的浓度。我们发现,无论治疗策略如何,腹水 EpCAM 阳性 EVs 浓度越高,无进展生存期(PFS)越短。我们还发现腹水和血浆中 EpCAM 阳性 EVs 浓度之间存在很强的相关性。我们的研究结果表明,晚期 HGSC 患者腹水 EpCAM 阳性 EVs 具有作为预测早期复发的预后生物标志物的潜力,从而可能具有更具侵袭性的肿瘤生物学和化疗耐药性的发展。

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