Exploration of Short-chain Fatty Acid-Associated Hub Genes and potential therapeutic targets in Primary Open-Angle Glaucoma

Abstract

Abstract Purpose Glaucoma is a progressive optic neuropathy with degeneration of retinal ganglion cells and retinal nerve fiber layer. Studies have shown that short chain fatty acids produced by gut microbiota can regulate intraocular inflammation. The aim of this research was to screen biomarkers associated with short chain fatty acids in glaucoma. Methods Firstly, WGCNA was performed for obtaining the key module genes associated with the primary open-angle glaucoma (POAG). We performed differential expression analysis (POAG samples vs normal samples) to obtain differentially expressed genes (DEGs) in GSE27276 dataset. The short chain fatty acids related differentially expressed genes (SCFAR-DEGs) were obtained by overlapping DEGs, short chain fatty acids related genes (SCFARGs) and key module genes. Three machine learning algorithms were implemented to select short chain fatty acids related biomarkers. We performed immune infiltration and GSEA based on biomarkers. Results A sum of 2433 key module genes associated with POAG were identified. We identified 615 DEGs between two groups. Soon afterwards, 10 SCFAR-DEGs were obtained through overlapping DEGs, SCFARGs and key module genes. Moreover, 5 biomarkers associated with short chain fatty acids, including HBB, ZFP36, NFKBIA, TIMP2 and NAMPT, were screened via three machine learning algorithms. The immune infiltration and GSEA analysis suggested that these biomarkers were related to the function of antigen presentation and some differential immune cells. Conclusion Overall, we obtained five short chain fatty acids related biomarkers (THBB, ZFP36, NFKBIA, TIMP2 and NAMPT) associated with POAG, which laid a theoretical foundation for the treatment of glaucoma.