A Predictive Model for Initial Platinum-Based Chemotherapy Efficacy in Patients with Postoperative Epithelial Ovarian Cancer Using Tissue-Derived Small Extracellular Vesicles

IF 15.5 1区 医学 Q1 CELL BIOLOGY
Shizhen Shen, Conghui Wang, Jiaxin Gu, Feifei Song, Xiaodong Wu, Fangfang Qian, Xiaojing Chen, Lingfang Wang, Qiaohua Peng, Ziyu Xing, Lingkai Gu, Fenfen Wang, Xiaodong Cheng
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Abstract

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.

Abstract Image

利用组织来源的细胞外小泡建立卵巢上皮癌术后患者初始铂类化疗疗效预测模型
上皮性卵巢癌(EOC)是一种经常致命的恶性肿瘤,其特点是对铂类化疗产生耐药性。因此,准确预测铂类药物的疗效对于战略性地选择术后干预措施以降低与次优治疗效果和不良反应相关的风险至关重要。组织来源的细胞外囊泡(tsEVs)与血浆来源的细胞外囊泡不同,是研究 EOC 组织独特属性的有力工具。在这项研究中,对从58名铂敏感和30名铂耐药的EOC患者体内获得的tsEV进行了4D数据独立采集(DIA)蛋白质组测序。分析结果表明,差异表达的蛋白质明显富集,这些蛋白质主要与免疫相关通路有关。此外,还通过 LASSO 回归确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筛选出的临床参数相结合,用于构建多变量逻辑回归模型。该模型将三个 tsEV IRPs(CCR1、IGHV_35 和 CD72)与一个临床参数(是否存在术后残留病灶)整合在一起。因此,该模型可以预测EOC患者术后初始铂类化疗的疗效,甚至在开始化疗之前就能提供预后信息。
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来源期刊
Journal of Extracellular Vesicles
Journal of Extracellular Vesicles Biochemistry, Genetics and Molecular Biology-Cell Biology
CiteScore
27.30
自引率
4.40%
发文量
115
审稿时长
12 weeks
期刊介绍: The Journal of Extracellular Vesicles is an open access research publication that focuses on extracellular vesicles, including microvesicles, exosomes, ectosomes, and apoptotic bodies. It serves as the official journal of the International Society for Extracellular Vesicles and aims to facilitate the exchange of data, ideas, and information pertaining to the chemistry, biology, and applications of extracellular vesicles. The journal covers various aspects such as the cellular and molecular mechanisms of extracellular vesicles biogenesis, technological advancements in their isolation, quantification, and characterization, the role and function of extracellular vesicles in biology, stem cell-derived extracellular vesicles and their biology, as well as the application of extracellular vesicles for pharmacological, immunological, or genetic therapies. The Journal of Extracellular Vesicles is widely recognized and indexed by numerous services, including Biological Abstracts, BIOSIS Previews, Chemical Abstracts Service (CAS), Current Contents/Life Sciences, Directory of Open Access Journals (DOAJ), Journal Citation Reports/Science Edition, Google Scholar, ProQuest Natural Science Collection, ProQuest SciTech Collection, SciTech Premium Collection, PubMed Central/PubMed, Science Citation Index Expanded, ScienceOpen, and Scopus.
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