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基于生物信息学和机器学习的急性胰腺炎脂质代谢相关关键生物标志物的鉴定及其调控机制

Identification of Key Biomarkers Related to Lipid Metabolism in Acute Pancreatitis and Their Regulatory Mechanisms Based on Bioinformatics and Machine Learning.

作者信息

Zhang Liang, Jiang Yujie, Jin Taojun, Zheng Mingxian, Yap Yixuan, Min Xuanyang, Chen Jiayue, Yuan Lin, He Feng, Zhou Bingduo

机构信息

Department of Gastroenterology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.

The Center for Cancer Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

出版信息

Biomedicines. 2025 Aug 31;13(9):2132. doi: 10.3390/biomedicines13092132.

Abstract

Acute pancreatitis (AP) is characterized by the abnormal activation of pancreatic enzymes due to various causes, leading to local pancreatic inflammation. This can trigger systemic inflammatory response syndrome and multi-organ dysfunction. Hyperlipidemia, mainly resulting from lipid metabolism disorders and elevated triglyceride levels, is a major etiological factor in AP. This study aims to investigate the role of lipid metabolism-related genes in the pathogenesis of AP and to propose novel strategies for its prevention and treatment. We obtained AP-related datasets GSE3644, GSE65146, and GSE121038 from the GEO database. Differentially expressed genes (DEGs) were identified using DEG analysis and gene set enrichment analysis (GSEA). To identify core lipid metabolism genes in AP, we performed least absolute shrinkage and selection operator (LASSO) regression and support vector machine recursive feature elimination (SVM-RFE) analysis. Gene and protein interactions were predicted using GeneMANIA and AlphaFold. Finally, biomarker expression levels were quantified using Real-Time quantitative Polymerase Chain Reaction (RT-qPCR) in an AP mouse model. Seven lipid metabolism-related genes were identified as key biomarkers in AP: , , , , , , and . The biological roles of these genes mainly involve fatty acid metabolism, cholesterol metabolism, lipid transport across cellular membranes, and mitochondrial function. , , , , , , and are characteristic biomarkers of lipid metabolism abnormalities in AP. These findings are crucial for a deeper understanding of lipid metabolism pathways in AP and for the early implementation of preventive clinical measures, such as the control of blood lipid levels.

摘要

急性胰腺炎(AP)的特征是由于各种原因导致胰腺酶异常激活,进而引发胰腺局部炎症。这可能会触发全身炎症反应综合征和多器官功能障碍。高脂血症主要由脂质代谢紊乱和甘油三酯水平升高引起,是AP的主要病因。本研究旨在探讨脂质代谢相关基因在AP发病机制中的作用,并提出新的预防和治疗策略。我们从基因表达综合数据库(GEO数据库)中获取了与AP相关的数据集GSE3644、GSE65146和GSE121038。使用差异基因分析和基因集富集分析(GSEA)来识别差异表达基因(DEGs)。为了识别AP中的核心脂质代谢基因,我们进行了最小绝对收缩和选择算子(LASSO)回归以及支持向量机递归特征消除(SVM-RFE)分析。使用基因互作网络分析工具(GeneMANIA)和阿尔法折叠(AlphaFold)预测基因和蛋白质相互作用。最后,在AP小鼠模型中使用实时定量聚合酶链反应(RT-qPCR)对生物标志物表达水平进行定量。七个脂质代谢相关基因被确定为AP中的关键生物标志物: 、 、 、 、 、 和 。这些基因的生物学作用主要涉及脂肪酸代谢、胆固醇代谢、跨细胞膜的脂质转运以及线粒体功能。 、 、 、 、 、 和 是AP中脂质代谢异常的特征性生物标志物。这些发现对于深入了解AP中的脂质代谢途径以及早期实施预防性临床措施(如控制血脂水平)至关重要。

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