PDF(Pubmed)
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癌（HGSC）是一种不治之症，因此,人们正在广泛寻找有助于及时调整治疗和个性化方法的生物标志物.可以从HGSC患者的腹水和血液中分离的肿瘤衍生的细胞外囊泡(EV)是如此有希望的生物标志物。上皮细胞粘附分子(EpCAM)表达在大多数上皮源性肿瘤中上调;然而,有关EpCAM过表达在卵巢癌中的预后价值的研究显示出矛盾的结果。我们研究的目的是评估总和EpCAM阳性EV作为晚期HGSC的预后和预测性生物标志物的潜力。流式细胞术用于确定37例接受不同一线治疗的晚期HGSC患者的配对预处理腹水和血浆样品中总和EpCAM阳性EV的浓度。我们发现，无论治疗策略如何，腹水中较高的EpCAM阳性EV浓度与较短的无进展生存期（PFS）有关。我们还发现腹水和血浆之间EpCAM阳性EV浓度的强相关性。我们的发现表明，晚期HGSC患者腹水中的EpCAM阳性EVs有可能作为预测早期复发的预后生物标志物，从而预测更具侵袭性的肿瘤生物学和化学耐药性的发展。
