Identification of Key Efferocytosis-Related Genes and Mechanisms in Diabetic Retinopathy

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.