Exploring the mechanisms of ferroptosis and immune infiltration in meniscus injuries at different age stages using machine learning
Objective:To identify key ferroptosis-related biomarkers and investigate immune infiltration in meniscus inju-ries among individuals of different age groups.Methods:(1)We obtained our training dataset from the GEO database and analyzed gene expression matrices from the GSE191157 gene chip dataset.Simultaneously,we downloaded relevant genes associated with ferroptosis for further analysis.(2)Using the"limma"package,we conducted differential gene expression analysis between elderly and young patients with meniscus injuries and performed weighted gene co-expression network analysis(WGCNA)on all genes in the GSE191157 gene chip dataset.(3)We selected two color modules most correlated with meniscus injury and then intersected the genes in these modules with ferroptosis-related genes.(4)Subsequently,we conducted ontology(GO)and Kyoto Encyclope-dia of Genes and Genomes(KEGG)analyses on the intersected genes.(5)Using LASSO regression in machine learning,we ana-lyzed the intersected genes related to ferroptosis in meniscus injuries among individuals of different ages and extracted core genes.(6)Finally,we conducted gene set enrichment analysis(GSEA)and single-sample gene set enrichment variation analysis(ssG-SEA)for immune infiltration and confirmed the correlation between core genes and ferroptosis in meniscus injuries.Results:A to-tal of 2 517 differentially expressed genes were identified,and the intersection of these genes with ferroptosis-related genes yielded 61 genes.After WGCNA analysis,the blue and yellow modules were found to be most relevant to the disease,resulting in 46 in-tersected genes.Through LASSO regression analysis,four core genes(BEX1,MMP13,PTPN18,and SLC38A1)were select-ed.GSEA results indicated that ferroptosis in meniscus injuries is primarily associated with Toll-like receptor signaling,RNA tran-scription and splicing,mTOR signaling,and ECM-receptor interaction.Immune cell infiltration analysis revealed a significant cor-relation between core gene expression and immune cell infiltration.MMP13 exhibited a negative correlation with effector memory CD8 T cells,CD56dim natural killer cells,and central memory CD4 T cells,while SLC38A1,BEX1,and PTPN18 were posi-tively correlated.Conclusion:This study identified four key genes associated with ferroptosis in meniscus injuries among individu-als of different age groups,namely BEX1,MMP13,PTPN18,and SLC38A1.Immune cell infiltration analysis demonstrated a clear correlation between core gene expression and immune cell infiltration.
万方数据
维普
