Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Department of Gynecologic Oncology, School of Medicine, Women's Hospital, Zhejiang University, Hangzhou, Zhejiang, China.
J Extracell Vesicles. 2024 Aug;13(8):e12486. doi: 10.1002/jev2.12486.
Epithelial ovarian cancer (EOC) is an often-fatal malignancy marked by the development of resistance to platinum-based chemotherapy. Thus, accurate prediction of platinum drug efficacy is crucial for strategically selecting postoperative interventions to mitigate the risks associated with suboptimal therapeutic outcomes and adverse effects. Tissue-derived extracellular vesicles (tsEVs), in contrast to their plasma counterparts, have emerged as a powerful tool for examining distinctive attributes of EOC tissues. In this study, 4D data-independent acquisition (DIA) proteomic sequencing was performed on tsEVs obtained from 58 platinum-sensitive and 30 platinum-resistant patients with EOC. The analysis revealed a notable enrichment of differentially expressed proteins that were predominantly associated with immune-related pathways. Moreover, pivotal immune-related proteins (IRPs) were identified by LASSO regression. These factors, combined with clinical parameters selected through univariate logistic regression, were used for the construction of a model employing multivariate logistic regression. This model integrated three tsEV IRPs, CCR1, IGHV_35 and CD72, with one clinical parameter, the presence of postoperative residual lesions. Thus, this model could predict the efficacy of initial platinum-based chemotherapy in patients with EOC post-surgery, providing prognostic insights even before the initiation of chemotherapy.
上皮性卵巢癌(EOC)是一种常致命的恶性肿瘤,其特征是对铂类化疗药物产生耐药性。因此,准确预测铂类药物的疗效对于有策略地选择术后干预措施以降低治疗效果不理想和不良反应相关风险至关重要。与血浆来源的外泌体相比,组织来源的细胞外囊泡(tsEVs)已成为研究 EOC 组织独特特征的有力工具。在这项研究中,对 58 例铂类敏感和 30 例铂类耐药的 EOC 患者的 tsEVs 进行了 4D 无依赖数据采集(DIA)蛋白质组学测序。分析显示,差异表达蛋白明显富集,这些蛋白主要与免疫相关途径有关。此外,通过 LASSO 回归鉴定了关键的免疫相关蛋白(IRPs)。这些因素与通过单变量逻辑回归选择的临床参数一起,用于构建多元逻辑回归模型。该模型整合了三个 tsEV IRPs(CCR1、IGHV_35 和 CD72)和一个临床参数(术后残留病灶的存在)。因此,该模型可以预测术后接受初始铂类化疗的 EOC 患者的疗效,甚至在开始化疗之前就能提供预后信息。