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利用与内质网应激相关基因检测糖尿病视网膜病变的诊断模型及综合检查

Detection of a Diagnostic Model and Comprehensive Examination of Diabetic Retinopathy Utilizing Genes Linked to Endoplasmic Reticulum Stress.

作者信息

Zhang Yan, Huang Yihong, Guo Maosheng, Chen Wanzhu, Wu Yuyu

机构信息

Department of Ophthalmology, Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, China.

出版信息

Endocr Metab Immune Disord Drug Targets. 2025;25(2):122-139. doi: 10.2174/0118715303300673240725114443.

Abstract

OBJECTIVES

The aim of this study was to reveal the biological functionalities associated with endoplasmic reticulum stress (ERS)-related genes (ERSGs) in the context of diabetic retinopathy (DR).

METHODS

Differentially expressed genes (DEGs) within the DR group and the Control group were identified and then integrated with ERSGs. Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) methodologies were used to investigate potential biological mechanisms. A diagnostic model for ERS and a nomogram were formulated based on biomarkers selected through the Least Absolute Shrinkage and Selection Operator method. The diagnostic efficacy of this model was thoroughly evaluated. ERS-associated subtypes were identified, and the Single-Sample GSEA (ssGSEA) and CIBERSORT algorithms were used to assess immune infiltration.

RESULTS

We identified 10 ERS-related DEGs (ERSRDEGs) within the DR Group. Subsequently, a diagnostic model was constructed based on 5 ERS genes, namely CCND1, IGFBP2, TLR4, TXNIP, and VIM. The validation analysis demonstrated the commendable diagnostic performance of the model. Analysis of the ssGSEA immune characteristics revealed a positive correlation in the DR group between myeloid-derived suppressor cells (MDSC), regulatory T cells (Tregs), and CCND1 TXNIP. Furthermore, a significant negative correlation was observed between central memory CD4 T cells and CCND1. In the context of CIBERSORT, the results indicated a positive correlation between macrophages and IGFBP2, as well as Tregs and IGFBP2 in the DR group. Notably, a conspicuous negative correlation was identified between resting mast cells and IGFBP2.

CONCLUSION

The present study provides novel diagnostic biomarkers for DR from an ERS perspective.

摘要

目的

本研究旨在揭示糖尿病视网膜病变(DR)背景下与内质网应激(ERS)相关基因(ERSGs)相关的生物学功能。

方法

鉴定DR组和对照组中的差异表达基因(DEGs),然后与ERSGs整合。使用基因本体论(GO)和基因集富集分析(GSEA)方法研究潜在的生物学机制。基于通过最小绝对收缩和选择算子方法选择的生物标志物,制定了ERS诊断模型和列线图。对该模型的诊断效能进行了全面评估。鉴定了与ERS相关的亚型,并使用单样本GSEA(ssGSEA)和CIBERSORT算法评估免疫浸润。

结果

我们在DR组中鉴定出10个与ERS相关的差异表达基因(ERSRDEGs)。随后,基于5个ERS基因构建了诊断模型,即CCND1、IGFBP2、TLR4、TXNIP和VIM。验证分析表明该模型具有良好的诊断性能。对ssGSEA免疫特征的分析显示,DR组中髓系来源的抑制细胞(MDSC)、调节性T细胞(Tregs)与CCND1、TXNIP之间呈正相关。此外,中央记忆CD4 T细胞与CCND1之间存在显著负相关。在CIBERSORT分析中,结果表明DR组中巨噬细胞与IGFBP2之间以及Tregs与IGFBP2之间呈正相关。值得注意的是,静息肥大细胞与IGFBP2之间存在明显的负相关。

结论

本研究从ERS角度为DR提供了新的诊断生物标志物。

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