基于生物信息学对肝硬化中核心基因的筛选及意义探究
投稿时间:2024-05-22  修订日期:2024-07-02  点此下载全文
引用本文:沈仕俊,邓翔,饶永凤,帕成周.基于生物信息学对肝硬化中核心基因的筛选及意义探究[J].医学研究杂志,2025,54(1):54-60
DOI: 10.11969/j.issn.1673-548X.2025.01.011
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作者单位
沈仕俊 临沧市人民医院肝胆胰微创外科 677099 
邓翔 临沧市人民医院肝胆胰微创外科 677099 
饶永凤 临沧市人民医院肝胆胰微创外科 677099 
帕成周 昆明医科大学附属甘美医院肝胆胰外科 650011 
基金项目:云南省科技厅重大科技专项计划项目(肝、肾器官移植关键技术研究与应用-202302AA310018);云南省昆明市卫生和健康委员会人才类项目[2023-sw(技)-27];云南省临沧市科协科技社团能力服务创新发展项目(202404);大理大学教育教学改革项目(JG09YX209)
中文摘要:目的 基于生物信息学筛选肝硬化疾病中的核心基因,构建核心基因相互作用网络,探究核心基因发挥作用的通路及其临床意义。方法 从GEO(gene expression omnibus data base)数据库中获取转录组数据集进行差异基因筛选,并进行基因本体(gene ontology,GO)分析及基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析,利用STRING(search tool for the retrieval of interacting genes/proteins)数据库构建蛋白互作网络,MCC算法筛选出前10位核心基因并建立miRNA-mRNA调控关系,新增GEO数据集及临床样本做核心基因表达验证,进行ROC分析评估临床意义。结果 本研究中筛选出47个上调基因,34个下调基因,差异基因参与细胞外基质组织、泌尿生殖系统发育、参与细胞对铜、镉、锌离子的反应调节等生物过程,通过ECM受体相互作用通路发挥功能。前10个核心基因为SPP1、SOX9、COL1A2、TAGLN、ACTA2、CCND1、CD24、VWF、JAG1、MMP7。核心基因在肝硬化组织中表达升高,且CCND1、CD24、VWF具有非常高的准确度区分肝硬化组织(AUC>0.90)。结论 肝硬化中核心基因在肝硬化组织中表达升高,可能通过ECM受体相互作用通路发挥功能促进肝纤维化,CCND1、CD24、VWF可能会成为肝硬化诊治的有效靶点。
中文关键词:肝硬化 核心基因 生物信息学 临床意义
 
Screening and Exploring the Significance of Core Genes in Liver Cirrhosis Based on Bioinformatics.
Abstract:Objective To identify the core genes in liver cirrhosis through bioinformatics screening, construct a network of their interactions, and explore the pathways and clinical significance of these genes. Methods Transcriptome datasets were obtained from the GEO database to screen for differential gene expression. GO analysis and KEGG pathway enrichment analysis were performed. A protein interaction network was constructed using the STRING database. The top 10 core genes were identified using the MCC algorithm, and the miRNA-mRNA regulatory relationships were established. The validation of the core gene expression was conducted with additional GEO datasets and clinical samples, and ROC analysis was used to evaluate the clinical significance. Results A total of 47 upregulated and 34downregulated genes were identified in this study. These differential genes were involved in biological processes such as extracellular matrix organization, urogenital system development, and cellular responses to copper, cadmium, and zinc ions. They performed the interaction pathway function through the ECM receptor. The top 10 core genes were SPP1, SOX9, COL1A2, TAGLN, ACTA2, CCND1, CD24, VWF, JAG1 and MMP7. The expression of the core genes was increased in cirrhotic tissues, among which CCND1, CD24 and VWF showed high accuracy in distinguishing the cirrhotic tissues (AUC > 0.90). Conclusion The expression of the core genes in liver cirrhosis is increased and may lead to liver fibrosis through the ECM receptor interaction pathway, while the CCND1, CD24 and VWF could serve as effective targets for the diagnosis and treatment of liver cirrhosis.
keywords:Cirrhosis  Core genes  Bioinformatics  Clinical significance
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