基于眼液蛋白质组学的多形性脉络膜血管病抗血管内皮生长因子治疗的反应性:初步研究。

IF 3 3区 医学 Q1 OPHTHALMOLOGY Acta Ophthalmologica Pub Date : 2024-10-18 DOI:10.1111/aos.16768
Yuelin Wang, Dongjun Xing, Jialiang Duan, Huiying Zhou, Lihui Meng, Shuang Geng, Huan Chen, Ruoan Han, Zhiqing Li, Jingxue Ma, Youxin Chen
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引用次数: 0

摘要

目的:多形性脉络膜血管病(PCV)患者对抗血管内皮生长因子疗法的反应存在差异。本研究旨在分析 PCV 患者的眼液蛋白质组图谱,为确定与抗血管内皮生长因子药物反应相关的生物标志物提供初步见解:方法:前瞻性地从北京和天津的两家医院招募未接受治疗或未接受治疗超过3个月的PCV患者。根据抗血管内皮生长因子治疗前后黄斑中心厚度(ΔCMT/基线-CMT)的相对变化,将 PCV 患者分为良好反应(GR)组(≤-25%)和不良反应(PR)组(>-25%)。采用数据独立获取-质谱(DIA-MS)方法进行了水液蛋白质组学研究,并对不同 PCV 组和对照组之间的差异表达蛋白质(DEPs)进行了分析。利用 Luminex 方法回顾性地筛选出关键的 DEPs,并对其在水液中的表达进行初步验证:共纳入 31 名 PCV 患者(31 只眼),其中 GR 组 13 人,PR 组 18 人。共鉴定出 414 个 DEPs,其中包括 36 个明显上调的蛋白质,如 G 蛋白调节因子 10 (RGS10)、podocin (PODN) 和表皮生长因子 (EGF),以及 32 个下调的蛋白质,包括 RAB11FIP4(Rab11 家族交互蛋白 4)、α-突触核蛋白 (SNCA)、血红蛋白亚基 δ (HBD) 和白细胞介素 6 (IL6)。与白内障对照组(10 只眼睛)相比,134 个蛋白质明显上调,72 个蛋白质下调。KEGG 通路富集分析显示,GR 组和 PR 组在细胞通讯和细胞信号传导方面存在差异。蛋白质-蛋白质相互作用分析表明,EGF 与各种 DEPs 之间存在相互作用。使用 Luminex 方法对水液蛋白进行验证后发现,EGF 水平的变化与 PCV 患者的抗血管内皮生长因子治疗反应有关:结论:抗血管内皮生长因子治疗反应良好或不良的 PCV 患者表现出不同的眼液蛋白质组特征。水样 EGF 可作为 PCV "精确治疗 "的生物标志物。
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Responsiveness of anti-VEGF treatment for polypoidal choroidal vasculopathy based on aqueous humour proteomics: A preliminary study.

Objectives: Patients with polypoidal choroidal vasculopathy (PCV) exhibit variability in response to anti-VEGF therapy. This study aimed to analyse the aqueous humour proteomic profiles of PCV patients and provide preliminary insights for the identification of biomarkers associated with anti-VEGF drug responsiveness.

Methods: PCV patients who were treatment-naïve or untreated for more than 3 months were prospectively recruited from two hospitals in Beijing and Tianjin. Based on the relative changes in central macular thickness (ΔCMT/baseline-CMT) before and after anti-VEGF treatment, the PCV patients were divided into a good response (GR) group (≤-25%) and a poor response (PR) group (>-25%). Aqueous humour proteomics was performed by the Data-independent Acquisition-Mass Spectrometry (DIA-MS) method, and differentially expressed proteins (DEPs) analysis between the different PCV groups and the control group was conducted. Key DEPs were selected for preliminary validation in the aqueous humour using the Luminex method retrospectively.

Results: A total of 31 PCV patients (31 eyes) were included, 13 in the GR group and 18 in the PR group. A total of 414 DEPs were identified, including 36 significantly upregulated proteins, such as G protein regulatory factor 10 (RGS10), podocin (PODN) and epidermal growth factor (EGF), and 32 downregulated proteins, including RAB11FIP4 (Rab11 family-interacting protein 4), α-synuclein (SNCA), haemoglobin subunit δ (HBD) and interleukin 6 (IL6). Compared to the cataract control group (10 eyes), 134 proteins were significantly upregulated, and 72 were downregulated. KEGG pathway enrichment analysis revealed that the GR and PR groups differ in terms of cell communication, and cell signal transduction. Protein-protein interaction analysis revealed interactions between EGF and various DEPs. Validation of aqueous humour proteins using the Luminex method revealed that changes in the levels of EGF were associated with the anti-VEGF treatment response in PCV patients.

Conclusions: PCV patients with good or poor anti-VEGF responses exhibit distinct aqueous humour proteomic profiles. Aqueous EGF may serve as a biomarker for the 'precise treatment' of PCV.

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来源期刊
Acta Ophthalmologica
Acta Ophthalmologica 医学-眼科学
CiteScore
7.60
自引率
5.90%
发文量
433
审稿时长
6 months
期刊介绍: Acta Ophthalmologica is published on behalf of the Acta Ophthalmologica Scandinavica Foundation and is the official scientific publication of the following societies: The Danish Ophthalmological Society, The Finnish Ophthalmological Society, The Icelandic Ophthalmological Society, The Norwegian Ophthalmological Society and The Swedish Ophthalmological Society, and also the European Association for Vision and Eye Research (EVER). Acta Ophthalmologica publishes clinical and experimental original articles, reviews, editorials, educational photo essays (Diagnosis and Therapy in Ophthalmology), case reports and case series, letters to the editor and doctoral theses.
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