Comprehensive Analysis of Glycolysis-Related Genes and Their Mechanisms in Diabetic Retinopathy

Objective This study aimed to screen glycolysis-related differentially expressed genes (DEGs) to identify the DEGs associated with diabetic retinopathy (DR), preliminarily elucidate their significance in DR, identify novel diagnostic biomarkers and therapeutic targets, and provide insights to improve the early diagnosis and treatment of patients with DR. Methods The DR expression profile datasets GSE122189 [1] and GSE146615 [2] were downloaded from the Gene Expression Omnibus (GEO) database. Glycolysis-related genes were curated from the GeneCards, MSigDB, and PubMed databases. By integrating glycolysis-related genes with DR patient data from GEO, differential expression analysis was performed to identify glycolysis-related DEGs. Subsequent analyses included Gene Ontology, KEGG, and Gene Set Enrichment Analysis, correlation analysis with immune cell infiltration, prediction of interacting miRNAs, identification of transcription factors (TFs) binding to glycolysis-related genes (GRGs), and screening of potential drugs or molecular compounds. Results Seven glycolysis-related DEGs were identified that were associated with DR: ANKRD1, ATP6V0C, CDC25C, HDLBP, LRP6, PKP1 , and ZFP36. These GRGs were significantly enriched in cellular components (CC), such as ficolin-1-rich granule membrane, tertiary granules, and ficolin-1-rich granules, as well as molecular functions (MF), including intermediate filament binding, titin binding, and low-density lipoprotein particle receptor activity. In dataset GSE122189, DEGs were enriched in the pathways of PEPPER_CHRONIC_LYMPHOCYTIC_LEUKEMIA_UP, WP_COVID19_ADVERSE_OUTCOME_PATHWAY, and WP_DEVELOPMENT_AND_HETEROGENEITY_OF_THE_ILC_FAMILY. In dataset GSE146615, DEGs were enriched in pathways such as KONG_E2F3_TARGETS, CROONQUIST_IL6_DEPRIVATION_DN, and TANG_SENESCENCE_TP53_TARGETS_DN. In the mRNA-TF interaction network, HDLBP exhibited the highest number of interactions (57 mRNA-TF pairs). Twenty-five drugs or molecular compounds targeting CASP1 were identified. Significant correlations (P < 0.05) were observed between the expression of the seven GRGs and immune cell infiltration levels: nine immune cell types in GSE122189 and 17 immune cell types in GSE146615. Conclusion The glycolysis-related DEGs ANKRD1, ATP6V0C, CDC25C, HDLBP, LRP6, PKP1 , and ZFP36 are associated with DR. These genes may play critical roles in cellular differentiation, energy metabolism, and immune regulation, offering potential avenues for advancing DR diagnosis and therapy.