Identification and Verification of Immune Metabolism-Related Biomarkers and Immune Infiltration Landscape for Pediatric Opsoclonus Myoclonus Ataxia Syndrome in Neuroblastoma

神经母细胞瘤儿童眼阵挛肌阵挛共济失调综合征免疫代谢相关生物标志物及免疫浸润图谱的鉴定与验证

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Abstract

PURPOSE: This study aims to screen immune metabolism-associated biomarkers for pediatric opsoclonus myoclonus ataxia syndrome (OMAS) in neuroblastoma. METHODS: Immune metabolism-related genes were retrieved from the GeneCards database. The differentially expressed immune metabolism-related genes in OMAS were identified by bioinformatics, immune infiltration, and WGCNA analyses. The diagnostic genes were screened by three machine learning algorithms and validated by ROC curve and nomogram model. Correlation between diagnostic genes and differential immune infiltrated cells, GSEA, and drug chemistry small-molecule analyses was performed. Lastly, validation was performed in eight paired clinical samples. RESULTS: Total 162 differentially immune metabolism-related genes were obtained. Four diagnostic genes were selected by machine learning methods. The predictive accuracy of biomarker genes for OMAS was determined by nomograms and calibration curves. The targeted drugs for the four diagnostic genes contained bardoxolone methyl, alogliptin, and teneligliptin. Finally, clinical validation showed TRAF3IP2, DPP4, and RIPK1 upregulation and KEAP1 downregulation, consistent with bioinformatics analysis. The predictive accuracy of biomarkers was validated by ROC curve in clinical samples. CONCLUSION: Four immune metabolism-associated diagnostic genes were identified, including TRAF3IP2, RIPK1, KEAP1, and DPP4 for OMAS.

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