Hu Bihuan, Xia Hui, Tian Peixuan, Li Xinbao, Yang Yu, Zhu Zixuan, Zhou Yajie, Liao Wang, Wang Shoakang, Yang Ligang, Sun Guiju, Sui Jing
Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China.
Research Institute for Environment and Health, Nanjing University of Information Science and Technology, Nanjing 210044, China.
Int J Mol Sci. 2025 Jun 25;26(13):6104. doi: 10.3390/ijms26136104.
Alcoholic liver disease (ALD) is a type of liver disease with complex pathogenic factors. In 2019, alcohol caused 11 million life-years to be lost globally, and the mortality rate has continued to rise. This study aims to explore the exclusive gene profile of AH and construct an mRNA-lncRNA regulatory network through an integrative analysis and database validation to reveal potential key biomarkers. We obtained expression data for alcoholic hepatitis from the GEO database; screened differentially expressed genes (DEGs) through a weighted gene co-expression network analysis (WGCNA); conducted a GO&KEGG analysis; and focused on the enrichment pathways for the top 20 genes. Hub genes were selected using cytoHubba and MCODE to construct the mRNA-lncRNA regulatory network, and key genes were confirmed using GSE167308 and GSE28619. We obtained 2552 differentially expressed mRNAs and 555 differentially expressed lncRNAs from three databases. Differentially expressed genes are mainly involved in pathways such as lipid metabolism disorders, complement activation, the activation of cancer-related pathways, the excessive activation of inflammatory immunity, and the initiation of cell adhesion and fibrosis. Based on the hub gene analysis, we screened out 43 key genes. By constructing the key mRNA-lncRNA-pathway network, we identified 12 mRNAs (AQP1, ELOVL7, ITPR3, KRT19, KRT23, LAMC2, MMP7, PROM1, SPINT1, STK39, TNFRSF21, and VTCN1) and 14 lncRNAs that play an important role in the occurrence and development of alcoholic hepatitis. To sum up, this article mainly expounds upon the key genes in the occurrence and development of alcoholic hepatitis. The key genes are mainly concentrated within signaling pathways such as metabolic pathways, fatty acid metabolism, and cancer pathways. Twelve differentially expressed mRNAs in the co-expression network can be used as biomarkers and intervention targets for the diagnosis and treatment of alcoholic hepatitis.
酒精性肝病(ALD)是一种致病因素复杂的肝脏疾病。2019年,酒精导致全球1100万人年生命损失,且死亡率持续上升。本研究旨在探索酒精性肝炎(AH)的独特基因谱,并通过综合分析和数据库验证构建mRNA-lncRNA调控网络,以揭示潜在的关键生物标志物。我们从GEO数据库获取酒精性肝炎的表达数据;通过加权基因共表达网络分析(WGCNA)筛选差异表达基因(DEGs);进行GO和KEGG分析;并聚焦前20个基因的富集通路。使用cytoHubba和MCODE选择枢纽基因构建mRNA-lncRNA调控网络,并使用GSE167308和GSE28619验证关键基因。我们从三个数据库中获得了2552个差异表达的mRNA和555个差异表达的lncRNA。差异表达基因主要参与脂质代谢紊乱、补体激活、癌症相关通路激活、炎症免疫过度激活以及细胞黏附和纤维化起始等通路。基于枢纽基因分析,我们筛选出43个关键基因。通过构建关键的mRNA-lncRNA-通路网络,我们鉴定出12个mRNA(水通道蛋白1、超长链脂肪酸延伸酶7、肌醇1,4,5-三磷酸受体3、角蛋白19、角蛋白23、层粘连蛋白γ2、基质金属蛋白酶7、促红细胞生成素产生肝细胞受体1、丝氨酸蛋白酶抑制剂Kazal型1、丝氨酸/苏氨酸蛋白激酶39、肿瘤坏死因子受体超家族21和VTCN1)和14个lncRNA在酒精性肝炎的发生发展中起重要作用。综上所述,本文主要阐述了酒精性肝炎发生发展中的关键基因。关键基因主要集中在代谢通路、脂肪酸代谢和癌症通路等信号通路中。共表达网络中的12个差异表达mRNA可作为酒精性肝炎诊断和治疗的生物标志物及干预靶点。