Integrative Analyses of Genes of Pediatric Non-alcoholic Fatty Liver Disease Associated with Energy Metabolism.

IF 2.5 4区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Digestive Diseases and Sciences Pub Date : 2024-11-04 DOI:10.1007/s10620-024-08702-4
Yijun Lin, Hong Ye, Yan Chen, Rui Zhang, Yuyun Chen, Weijie Ou
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Abstract

Background: Pediatric non-alcoholic fatty liver disease (NAFLD) is a chronic steatosis of the liver associated with energy metabolism in children and adolescents, failure to intervene promptly can elevate the risk of developing hepatocellular carcinoma. Therefore, this study aimed to understand the underlying mechanism of pediatric NAFLD and investigate potential biomarkers and therapeutic targets.

Methods: We investigated genes using the GSE185051 data set related to energy metabolism from the GeneCards database, constructed protein-protein interaction network, identified hub genes and established networks representing interactions between these hub genes and miRNA, RNA-binding proteins, transcription factors, and drugs. Subsequently, we performed Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis, Gene Set Enrichment Analysis (GSEA), and immune infiltration analysis.

Results: Our analysis identified 9 hub genes through the PPI network. The target molecules were identified through the interaction network between hub genes and miRNAs, RNA-binding proteins, transcription factors, and drugs. GO analysis revealed that hub genes were associated with oxidative stress responses and other pathways. KEGG analysis highlighted their involvement in pathways such as insulin resistance, among others. GSEA revealed that hub genes were highly enriched in pathways related to Omega-9 fatty acid synthesis, among others. Immune infiltration analysis suggested that mast cells and T follicular helper cells play significant roles in the pathogenesis of NAFLD.

Conclusion: We identified the hub genes in pediatric NAFLD closely related to energy metabolism. These findings offer the potential for identifying potential novel diagnostic biomarkers, and establishing therapeutic targets for pediatric NAFLD.

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小儿非酒精性脂肪肝与能量代谢相关基因的综合分析。
背景:小儿非酒精性脂肪性肝病(NAFLD)是一种与儿童和青少年能量代谢相关的慢性肝脏脂肪变性,如果不能及时干预,会增加患肝细胞癌的风险。因此,本研究旨在了解小儿非酒精性脂肪肝的潜在机制,并研究潜在的生物标志物和治疗靶点:我们利用GeneCards数据库中与能量代谢相关的GSE185051数据集调查了基因,构建了蛋白-蛋白相互作用网络,确定了中心基因,并建立了代表这些中心基因与miRNA、RNA结合蛋白、转录因子和药物之间相互作用的网络。随后,我们进行了基因本体(GO)、京都基因组百科全书(KEGG)功能富集分析、基因组富集分析(GSEA)和免疫浸润分析:结果:我们通过 PPI 网络分析发现了 9 个枢纽基因。通过枢纽基因与 miRNA、RNA 结合蛋白、转录因子和药物之间的相互作用网络确定了靶分子。GO分析显示,中心基因与氧化应激反应和其他通路有关。KEGG 分析强调了这些基因参与了胰岛素抵抗等通路。GSEA显示,中枢基因高度富集于与Omega-9脂肪酸合成等相关的通路中。免疫浸润分析表明,肥大细胞和T滤泡辅助细胞在非酒精性脂肪肝的发病机制中发挥着重要作用:结论:我们发现了小儿非酒精性脂肪肝中与能量代谢密切相关的枢纽基因。结论:我们发现了小儿非酒精性脂肪肝中与能量代谢密切相关的枢纽基因,这些发现为确定潜在的新型诊断生物标志物和确立小儿非酒精性脂肪肝的治疗靶点提供了可能。
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来源期刊
Digestive Diseases and Sciences
Digestive Diseases and Sciences 医学-胃肠肝病学
CiteScore
6.40
自引率
3.20%
发文量
420
审稿时长
1 months
期刊介绍: Digestive Diseases and Sciences publishes high-quality, peer-reviewed, original papers addressing aspects of basic/translational and clinical research in gastroenterology, hepatology, and related fields. This well-illustrated journal features comprehensive coverage of basic pathophysiology, new technological advances, and clinical breakthroughs; insights from prominent academicians and practitioners concerning new scientific developments and practical medical issues; and discussions focusing on the latest changes in local and worldwide social, economic, and governmental policies that affect the delivery of care within the disciplines of gastroenterology and hepatology.
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