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基于蛋白质组和转录组分析鉴定早产儿视网膜病变潜在的泪液生物标志物。

Identifying potential tear biomarkers in premature infants with retinopathy of prematurity based on proteome and transcriptome analysis.

作者信息

Wu Dongting, Fan Zixin, Hu Yarou, Chen Yi, Tian Ruyin, Wang Cui, He Honghui, Yang Yuhang, Zhang Guoming

机构信息

State Key Laboratory of Ophthalmology, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, 510060, China.

Shenzhen Eye Hospital, Shenzhen Eye Medical Center, Southern Medical University, Shenzhen, 518040, Guangdong, China.

出版信息

Graefes Arch Clin Exp Ophthalmol. 2025 May 9. doi: 10.1007/s00417-025-06838-1.

Abstract

AIM

To identify the potential tear fluid biomarkers in premature infants with and without retinopathy of prematurity (ROP) based on proteomic and transcriptomic analysis.

METHODS

Tears were collected from the 46 eyes of the 23 enrolled premature infants, with and without ROP. Data-independent acquisition (DIA) mass spectrometry was utilized for the quantitative proteomic analysis of the two groups. Two published transcriptome datasets involving mouse oxygen-induced retinopathy (OIR) model data were selected from the Gene Expression Omnibus (GEO) database. iDEP (integrated Differential Expression and Pathway analysis) were used for differential expression analysis. Gene Ontology (GO)-based functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed.

RESULTS

In this study, a total of 1742 proteins were quantified from the two groups. 55 differentially expressed proteins closely related to immune and angiogenesis processes were identified, including 33 highly expressed as well as 22 lowly expressed in the ROP group. Combined with RNA-seq data from OIR model, we screened two particularly critical proteins, LYN and filamin A (FLNA), which were both expressed at significantly elevated levels.

CONCLUSIONS

According to the findings of the tear proteomics data, we hypothesized two particularly critical proteins, LYN and FLNA, may serve as pivotal regulators of immune and angiogenesis processes in ROP. These results will assist in the provision of new potential targets for the diagnosis of ROP.

摘要

目的

基于蛋白质组学和转录组学分析,鉴定患有和未患早产儿视网膜病变(ROP)的早产儿潜在的泪液生物标志物。

方法

收集23名纳入研究的早产儿的46只眼睛的泪液,其中包括患有和未患ROP的婴儿。采用数据非依赖采集(DIA)质谱法对两组进行定量蛋白质组分析。从基因表达综合数据库(GEO)中选择两个已发表的涉及小鼠氧诱导视网膜病变(OIR)模型数据的转录组数据集。使用iDEP(综合差异表达和通路分析)进行差异表达分析。进行基于基因本体(GO)的功能和京都基因与基因组百科全书(KEGG)通路富集分析。

结果

在本研究中,两组共定量了1742种蛋白质。鉴定出55种与免疫和血管生成过程密切相关的差异表达蛋白,其中ROP组中33种高表达,22种低表达。结合来自OIR模型的RNA测序数据,我们筛选出两种特别关键的蛋白质,即LYN和细丝蛋白A(FLNA),它们的表达水平均显著升高。

结论

根据泪液蛋白质组学数据的结果,我们推测两种特别关键的蛋白质LYN和FLNA可能是ROP免疫和血管生成过程的关键调节因子。这些结果将有助于为ROP的诊断提供新的潜在靶点。

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