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潜在铁死亡和非酒精性脂肪性肝病生物标志物的生物信息学分析。

Bioinformatics analysis of potential ferroptosis and non-alcoholic fatty liver disease biomarkers.

机构信息

Department of General Surgery, Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.

出版信息

Gen Physiol Biophys. 2024 Sep;43(5):371-384. doi: 10.4149/gpb_2024017.

Abstract

Ferroptosis plays a crucial role in the development of non-alcoholic fatty liver disease (NAFLD). In this study, we aimed to use a comprehensive bioinformatics approach and experimental validation to identify and verify potential ferroptosis-related genes in NAFLD. We downloaded the microarray datasets for screening differentially expressed genes (DEGs) and identified the intersection of these datasets with ferroptosis-related DEGs from the Ferroptosis database. Subsequently, ferroptosis-related DEGs were obtained using SVM analysis; the LASSO algorithm was then used to identify six marker genes. Furthermore, the CIBERSORT algorithm was used to estimate the proportion of different types of immune cells. Subsequently, we constructed drug regulatory networks and ceRNA regulatory networks. We identified six genes as marker genes for NAFLD, demonstrating their robust diagnostic abilities. Subsequent functional enrichment analysis results revealed that these marker genes were associated with multiple diseases and play a key role in NAFLD via the regulation of immune response and amino acid metabolism, among other pathways. The expression of hepatic EGR1, IL-6, SOCS1, and NR4A1 was significantly downregulated in the NAFLD model. Our findings provide new insights and molecular clues for understanding and treating NAFLD. Further studies are needed to assess the diagnostic potential of these markers for NAFLD.

摘要

铁死亡在非酒精性脂肪性肝病(NAFLD)的发展中起着至关重要的作用。在这项研究中,我们旨在使用综合的生物信息学方法和实验验证来鉴定和验证 NAFLD 中潜在的铁死亡相关基因。我们下载了用于筛选差异表达基因(DEGs)的微阵列数据集,并从 Ferroptosis 数据库中鉴定出这些数据集与铁死亡相关 DEGs 的交集。随后,使用 SVM 分析获得铁死亡相关 DEGs;然后使用 LASSO 算法识别出六个标记基因。此外,使用 CIBERSORT 算法估计不同类型免疫细胞的比例。随后,我们构建了药物调控网络和 ceRNA 调控网络。我们确定了六个基因作为 NAFLD 的标记基因,证明了它们具有稳健的诊断能力。随后的功能富集分析结果表明,这些标记基因与多种疾病相关,并通过调节免疫反应和氨基酸代谢等途径在 NAFLD 中发挥关键作用。在 NAFLD 模型中,肝组织 EGR1、IL-6、SOCS1 和 NR4A1 的表达明显下调。我们的研究结果为理解和治疗 NAFLD 提供了新的见解和分子线索。需要进一步研究来评估这些标记物对 NAFLD 的诊断潜力。

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