BackgroundAge-related macular degeneration (AMD) is a prevalent source of visual impairment among the elderly population, and its incidence has risen in tandem with the increasing longevity of humans. Despite the progress made in anti-VEGF therapy, the clinical outcomes have proven to be unsatisfactory.
MethodWe obtained differentially expressed genes (DEGs) of AMD patients and healthy controls from GEO database. GO analysis and KEGG analysis were used to enrich the differential genes. Weighted gene coexpression network analysis (WCGNA) is used to screen modules related to AMD expression. SVM, random forest, and least absolute shrinkage and selection operator (LASSO) were used to screen hub gene. Gene set enrichment analysis (GSEA) is used to explore the pathway through which these hub genes are enriched. CIBERSORT was used to analyze the relationship between hub gene and immune cell in ltration. Finally, West blotting and RT-PCR were used to explore the expression of Hub gene in AMD mice.
ResultsWe screened 1084 differential genes in GSE29801, of which 496 genes were up-regulated. 1084 differential genes were introduced into WCGNA analysis, and 94 genes related to AMD were obtained. 79 overlapping genes were obtained by VEEN plot. The 79 genes were introduced into three machine learning methods to screen the Hub gene, and the gene screened by the three methods was TNC,FAP,SREBF1,and TGF-β2. We veri ed their diagnostic function in GSE29801 and GSE103060 gene sets respectively. Then the pathway of hub gene co-enrichment was obtained by GO analysis and KEGG analysis. CIBERSORT analysis showed that these hub genes were associated with immune cell in ltration. Finally, we found increased expression of TNC, FAP, SREBF1, and TGF-β2 mRNA and protein in the retina of AMD mice.
ConclusionWe found that four hub genes, FAP, TGF-β2 and SREBF1,and TNC, have diagnostic signi cance in patients with AMD and are related to immune cell in ltration. Finally, we found up-regulated of these hub genes mRNA and protein in the retina of AMD mice.
