Table2_Use of a ferroptosis-related gene signature to construct diagnostic and prognostic models for assessing immune infiltration in metabolic dysfunction-associated fatty liver disease.docx

Introduction: Metabolic dysfunction-associated fatty liver disease (MAFLD), a serious health problem worldwide, can involve ferroptosis. This study aimed to comprehensively analyze the ferroptosis-related genes associated with MAFLD.
Methods: Ferroptosis-related differentially expressed genes (FRDEGs) were identified in patients with MAFLD and healthy individuals. Gene ontology functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and gene set enrichment analysis (GSEA) were used to analyze the relevant action pathways of the FRDEGs. The Encyclopedia of RNA Interactomes, CHIPBase, and comparative toxicogenomics databases were used to build mRNA-miRNA, mRNA-transcription factor (TF), and mRNA-drug interaction networks, respectively. A diagnostic model was constructed and bioinformatics analysis methods, such as least absolute shrinkage and selection operator regression analysis, Cox regression analysis, nomogram-based analysis, consensus clustering analysis, and single-sample GSEA, were used to systematically investigate the prognostic values and immunologic characteristics.
Results: A total of 13 FRDEGs were obtained and eight were used to construct a diagnostic model and perform a prognostic analysis. Hub genes were also used to construct mRNA-miRNA and mRNA-TF interaction networks and potential drug or molecular compounds. Two MAFLD subtypes were identified: cluster2, which represents an “immunoactive” type, and cluster1, which represents an “immunosuppressive” type; a significant correlation was observed between the immune cell contents and the expression of three FRDEGs (NR4A1, FADS2, and SCD).
Conclusion: A ferroptosis-related gene signature was constructed to diagnose MAFLD-associated steatohepatitis, predict the prognosis of MAFLD patients, and analyze the immunologic characteristics of MAFLD. Our findings may provide insights into developing innovative MAFLD treatment techniques.

引言：代谢功能障碍相关性脂肪性肝病（Metabolic dysfunction-associated fatty liver disease, MAFLD）是全球范围内亟待解决的重大健康问题，其发病机制涉及铁死亡（ferroptosis）。本研究旨在全面解析与MAFLD相关的铁死亡相关基因。
方法：本研究在MAFLD患者与健康个体中筛选得到铁死亡相关差异表达基因（Ferroptosis-related differentially expressed genes, FRDEGs）。通过基因本体（Gene Ontology, GO）功能富集分析、京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）通路富集分析及基因集富集分析（gene set enrichment analysis, GSEA），对FRDEGs的潜在作用通路进行解析。分别借助RNA互作组百科全书（Encyclopedia of RNA Interactomes）、CHIPBase数据库及比较毒理基因组学数据库，构建mRNA-miRNA、mRNA-转录因子（transcription factor, TF）及mRNA-药物互作网络。本研究构建了诊断模型，并采用最小绝对收缩和选择算子回归分析、Cox回归分析、列线图分析、一致性聚类分析及单样本GSEA等多种生物信息学分析方法，系统探究了相关基因的预后价值与免疫特征。
结果：本研究共筛选得到13个FRDEGs，其中8个用于构建诊断模型并开展预后分析。核心基因被用于构建mRNA-miRNA、mRNA-TF互作网络及潜在药物/分子化合物筛选体系。共鉴定出两种MAFLD亚型：簇2（cluster2）为"immunoactive"型，簇1（cluster1）为"immunosuppressive"型；免疫细胞浸润水平与3个FRDEGs（NR4A1、FADS2及SCD）的表达水平存在显著相关性。
结论：本研究构建了铁死亡相关基因特征，可用于诊断MAFLD相关性脂肪性肝炎、预测MAFLD患者预后及分析MAFLD的免疫特征。本研究结果可为开发创新性MAFLD治疗手段提供理论依据。