Table1_Identification of immune-related endoplasmic reticulum stress genes in proliferative diabetic retinopathy using bioinformatics analysis.xlsx

BackgroundProliferative diabetic retinopathy (PDR) is a severe complication of diabetes, and understanding its molecular mechanisms is crucial. Endoplasmic reticulum (ER) stress has been implicated in various diseases, including diabetic complications. This study aims to elucidate ER stress-related biomarkers in PDR, providing insights into the underlying molecular pathways.MethodsWe analyzed two independent PDR datasets, GSE102485 and GSE60436. The GSE102485 dataset (22 PDR and 3 normal samples) was the primary dataset for comprehensive analyses, including differential expression, functional enrichment, PPI network construction, immune cell infiltration, and drug prediction. The GSE60436 dataset (6 PDR and 3 normal samples) was used for validation. In vitro experiments using human umbilical vein endothelial cells (HUVECs) in a high-glucose environment were conducted to validate key bioinformatics outcomes. Western blotting assessed protein levels of ER stress markers (TRAM1 and TXNIP).ResultsDifferential expression analysis identified 2451 genes, including 328 ER stress-related genes. Functional analysis revealed enrichment in ER stress-related processes and pathways. Hub genes (BCL2, CCL2, IL-1β, TLR4, TNF, TP53) were identified, and immune infiltration analysis showed altered immune cell proportions. Validation in GSE60436 and in vitro confirmed ER stress gene dysregulation. Drug prediction suggested potential small molecules targeting ER stress markers.ConclusionThis study provides a comprehensive molecular characterization of ER stress in PDR, highlighting altered biological processes, immune changes, and potential therapeutic targets. The identified hub genes and small molecules offer avenues for further investigation and therapy development, enhancing understanding of PDR pathogenesis and aiding targeted intervention creation.

背景：增殖性糖尿病视网膜病变（PDR）是糖尿病的一种严重并发症，对其分子机制的深入理解至关重要。内质网（ER）应激与多种疾病，包括糖尿病并发症有关。本研究旨在阐明PDR中与ER应激相关的生物标志物，从而揭示潜在的分子通路。方法：我们分析了两个独立的PDR数据集，GSE102485和GSE60436。GSE102485数据集（22个PDR样本和3个正常样本）作为主要数据集，用于全面分析，包括差异表达、功能富集、PPI网络构建、免疫细胞浸润和药物预测。GSE60436数据集（6个PDR样本和3个正常样本）用于验证。在高糖环境下，我们使用人脐静脉内皮细胞（HUVECs）进行体外实验，以验证关键的生物信息学结果。Western blotting检测了ER应激标志物（TRAM1和TXNIP）的蛋白水平。结果：差异表达分析鉴定出2451个基因，包括328个与ER应激相关的基因。功能分析揭示了ER应激相关过程和通路的富集。中心基因（BCL2、CCL2、IL-1β、TLR4、TNF、TP53）被鉴定出来，免疫浸润分析显示免疫细胞比例发生改变。GSE60436和体外验证证实了ER应激基因失调。药物预测提出了针对ER应激标志物的潜在小分子。结论：本研究对PDR中的ER应激进行了全面的分子表征，突出了生物过程的改变、免疫变化和潜在的治疗靶点。所鉴定的中心基因和小分子为进一步的调查和治疗开发提供了途径，增强了我们对PDR发病机制的理解，并有助于靶向干预措施的创作。