Qian Yu, Jia Yanwen
Department of Ophthalmology, The First People's Hospital of Zhaoqing, 9 Donggang East Road, Zhaoqing, 526060, Guangdong, China.
Department of Ophthalmology, Changzhou Second People's Hospital Affiliated Nanjing Medical University, Changzhou, 213004, Jiangsu, China.
Mol Biotechnol. 2025 Jul;67(7):2785-2797. doi: 10.1007/s12033-024-01239-x. Epub 2024 Jul 31.
This study aimed to explore the key efferocytosis-related genes in diabetic retinopathy (DR) and their regulatory mechanisms. Public DR-related gene expression datasets, GSE160306 (training) and GSE60436 (validation), were downloaded. Differentially expressed efferocytosis-related genes (DEERGs) were analyzed using differential expression analysis and weighted gene co-expression network analysis. Functional enrichment analysis was conducted. Moreover, efferocytosis-related signature genes were identified using machine learning analysis, and their expression levels and diagnostic value were analyzed. Furthermore, nomograms were constructed; immune cell infiltration was analyzed; and gene set enrichment analysis, transcriptional regulation analysis, and small-molecule drug (SMD) prediction of efferocytosis-related signature genes were performed. In total, 36 DEERGs were identified in DR, and were markedly enriched in multiple functions, such as visual system development. Through further machine learning analysis, two efferocytosis-related signature genes, Ferritin Light Chain (FTL) and Fc Gamma Binding Protein (FCGBP), were identified, and were found to be upregulated in DR samples and showed high diagnostic performance for DR. A nomogram constructed using FTL and FCGBP accurately predicted the risk of DR. Moreover, the level of infiltration of immature B cells was positively correlated with FTL and FCGBP expression levels. Multiple transcription factors (TFs), such as CCCTC-Binding Factor (CTCF) and KLF Transcription Factor 9 (KLF9), were found to interact with both FTL and FCGBP. In addition, FTL can be targeted by miRNAs, such as miR-22-3p, and FCGBP can be targeted by miR-7973. In addition, both FTL and FCGBP can be targeted by SMDs, such as bisphenol A. Key efferocytosis-related genes, such as FTL and FCGBP, may promote DR development. Detecting or targeting FTL and FCGBP may aid in the prevention, diagnosis, and treatment of DR.
本研究旨在探索糖尿病视网膜病变（DR）中与胞葬作用相关的关键基因及其调控机制。下载了与DR相关的公共基因表达数据集GSE160306（训练集）和GSE60436（验证集）。使用差异表达分析和加权基因共表达网络分析对差异表达的胞葬作用相关基因（DEERGs）进行分析。进行了功能富集分析。此外，使用机器学习分析鉴定了与胞葬作用相关的特征基因，并分析了它们的表达水平和诊断价值。此外，构建了列线图；分析了免疫细胞浸润情况；并对与胞葬作用相关的特征基因进行了基因集富集分析、转录调控分析和小分子药物（SMD）预测。在DR中总共鉴定出36个DEERGs，它们在多种功能中显著富集，如视觉系统发育。通过进一步的机器学习分析，鉴定出两个与胞葬作用相关的特征基因，即铁蛋白轻链（FTL）和Fcγ结合蛋白（FCGBP），发现它们在DR样本中上调，并对DR具有较高的诊断性能。使用FTL和FCGBP构建的列线图准确预测了DR的风险。此外，未成熟B细胞的浸润水平与FTL和FCGBP的表达水平呈正相关。发现多个转录因子（TFs），如CCCTC结合因子（CTCF）和KLF转录因子9（KLF9），与FTL和FCGBP都相互作用。此外，FTL可被miR-22-3p等miRNA靶向，FCGBP可被miR-7973靶向。此外，FTL和FCGBP都可被双酚A等SMD靶向。FTL和FCGBP等关键的胞葬作用相关基因可能促进DR的发展。检测或靶向FTL和FCGBP可能有助于DR的预防、诊断和治疗。
