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用于卵巢癌诊断的液体活检中血清外泌体蛋白ZNF587B的筛选与鉴定

Screening and identification of serum exosomal protein ZNF587B in liquid biopsy for ovarian cancer diagnosis.

作者信息

Li Hu, Sui Tiantian, Chen Xiaoxiao, Gu Yanqiong, Luo Xuezhen, Liu Yiyao, He Qizhi

机构信息

Department of Pathology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University Shanghai 201204, China.

Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University Shanghai 200011, China.

出版信息

Am J Cancer Res. 2024 Apr 15;14(4):1904-1913. doi: 10.62347/RBTM1834. eCollection 2024.

Abstract

Addressing the critical challenge of early ovarian cancer (OC) detection, our study focuses on identifying novel biomarkers by analyzing preoperative peripheral blood exosomes from high-grade serous ovarian cancer (HGSC) patients and healthy controls. Utilizing high-performance liquid chromatography-mass spectrometry-based quantitative proteomics, we isolated and analyzed peripheral blood exosomes to identify differentially expressed proteins (DEPs). This comprehensive analysis, supported by gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) database assessments, revealed 28 proteins with decreased abundance and 33 with increased abundance in HGSC patients compared to controls. Notably, Zinc Finger Protein 587B (ZNF587B) exhibited a significant reduction in abundance, confirmed by decreased mRNA and protein levels in HGSC and normal ovarian tissues, consistent with omes exosomal protein expression levels. Immunohistochemical staining further confirmed reduced ZNF587B protein levels in HGSC tissues. The significant correlation between ZNF587B expression levels and tumor stage underscores its potential as a valuable biomarker for early liquid biopsy screening of OC. Our findings suggest ZNF587B plays a crucial role in early HGSC detection, highlighting the importance of further research to validate its clinical utility and improve ovarian cancer patient outcomes.

摘要

为应对早期卵巢癌(OC)检测这一关键挑战,我们的研究聚焦于通过分析高级别浆液性卵巢癌(HGSC)患者和健康对照者术前外周血外泌体来鉴定新型生物标志物。利用基于高效液相色谱 - 质谱的定量蛋白质组学技术,我们分离并分析了外周血外泌体,以鉴定差异表达蛋白(DEP)。通过基因本体富集分析和京都基因与基因组百科全书(KEGG)数据库评估支持的这项综合分析显示,与对照组相比,HGSC患者中有28种蛋白丰度降低,33种蛋白丰度增加。值得注意的是,锌指蛋白587B(ZNF587B)的丰度显著降低,HGSC和正常卵巢组织中的mRNA和蛋白水平降低证实了这一点,这与外泌体蛋白表达水平一致。免疫组织化学染色进一步证实HGSC组织中ZNF587B蛋白水平降低。ZNF587B表达水平与肿瘤分期之间的显著相关性强调了其作为OC早期液体活检筛查有价值生物标志物的潜力。我们的研究结果表明ZNF587B在早期HGSC检测中起关键作用,突出了进一步研究以验证其临床效用并改善卵巢癌患者预后的重要性。

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