Exploration of Lactylation-related Genes and Potential Mechanism in Diabetic Retinopathy

Previous studies have suggested that Diabetic Retinopathy (DR) may be linked to disturbed lactate homeostasis, but the exact mechanism remains unclear. In this study, we explored biomarkers related to DR and provided insights into their mechanisms based on Lactylation-Related Genes (LRGs).

The GSE185011, GSE60436, and LRGs were employed in this study. Firstly, the differentially expressed genes 1 (DEGs 1) and DEGs 2 were obtained by differential analysis in two datasets, respectively. Then, the common DEGs (CO-DEGs) were selected by integrating the intersection of up-regulated genes from DEGs 1 and DEGs 2, and the down-regulated genes from DEGs 1 and DEGs 2. Next, the candidate biomarkers were identified by overlapping the CO-DEGs and LRGs. Importantly, the biomarkers were further identified using expression analysis. Eventually, based on the biomarkers, GeneMANIA, function enrichment, subcellular localization, and related network analyses of the biomarkers were performed, respectively.

In this study, 7 candidate biomarkers were identified by overlapping the 262 CO-DEGs and 331 LRGs, all of which exhibited significantly consistent expression trends in GSE185011 and GSE60436. Therefore, they (RECQL, NOC3L, SSB, DDX18, ARID3B, LSP1, TKT) were defined as biomarkers. In GeneMANIA analysis, 20 genes with similar functions were predicted, such as DDX18-GNL2 and SSB-CDC27, which were mainly involved in ribosomal biosynthesis, rRNA metabolic process, etc. Later, function enrichment analysis revealed that biomarkers, except for RECQL, were enriched in ribosome, complement, and coagulation cascade pathways in GSE185011. Additionally, all biomarkers were rich in oxidative phosphorylation, Butanoate metabolism, and other pathways in GSE60436. For subcellular location analysis, ARID3B, DDX18, NOC3L, RECQL, and SSB may be located in the cytoplasm, while LSP1 and TKT might be located in the nucleus. Furthermore, TKT-pentose phosphate pathway genes (PGM2, TALDO1), and SSB-systemic lupus erythematosus genes (SNRPD1, SNRPD3, SNRPB) networks were separately constructed. Meanwhile, a disease-biomarkers-drugs was also built, such as Lipid Metabolism Disorders-NOC3L-Acetaminophen.

In this study, RECQL, NOC3L, SSB, DDX18, ARID3B, LSP1, and TKT were identified as biomarkers related to lactylation for DR, which provided a theoretical basis for the study of DR.