鉴定出参与大隐静脉曲张的核心基因:生物信息学分析  

Identification of key genes in great saphenous varicose veins:a bioinformatics analysis

作　　者：吴楠 谢春杨 WU Nan;XIE Chunyang(Department of General Surgery,The Fourth Affiliated Hospital of Harbin Medical University,Harbin 150023,P.R.China)

机构地区：[1]哈尔滨医科大学附属第四医院普外六病房,哈尔滨150023

出　　处：《中国普外基础与临床杂志》2025年第2期227-231,共5页Chinese Journal of Bases and Clinics In General Surgery

摘　　要：目的通过生物信息学方法鉴定参与大隐静脉曲张(great saphenous varicosis veins,GSVVs)的核心基因。方法从基因表达综合数据库中下载GSVVs组织与正常大隐静脉组织(对照组织)的转录组数据,通过单样本基因集富集分析计算Hallmark评分,使用加权基因共表达网络分析结合机器学习算法筛选与GSVVs相关的关键基因。使用String数据库进行蛋白-蛋白互作分析,受试者操作特征曲线判断目的基因对于GSVVs发生的区分能力。结果基因差异分析结果表明,与对照组织相比,GSVVs组织中上调基因548个、下调基因706个。单样本基因集富集分析结果显示,与对照组织相比,GSVVs组织中KRAS信号和顶端节点的Hallmark评分下调,而过氧化物酶体、凝血、活性氧途径等的Hallmark评分上调。加权基因共表达网络分析获得639个与GSVVs有关的差异基因。蛋白-蛋白互作分析发现372个基因所编码蛋白的165条互作关系,介数中心性值最高的前10个基因ADAM10、APP、NCBP2、SP1、ASB6、ADCY4、HP、UBE2C、QSOX1和CXCL1代表处于互作关系较为中心的位置,这些核心基因的功能富集分析显示主要与铜离子稳态、中性粒细胞脱颗粒作用G蛋白偶联受体信号、对氧化应激反应和酰胺代谢过程调节有关。将LASSO回归和支持向量机-相对误差过滤分析所得Hub基因进行交集发现SP1和QSOX1在两种算法中均为Hub基因。GSVVs组织中SP1和QSOX1表达均较在对照组织中显著上调,SP1和QSOX1在区分GSVVs组织和正常组织时受试者操作特征曲线下面积分别为0.972和1.000。结论SP1和QSOX1是GSVVs发生及发展过程中的核心基因,对SP1和QSOX1基因进行调控,有望实现对GSVVs的精准治疗。Objective To identify the core genes involved in the great saphenous varicose veins(GSVVs)through bioinformatics method.Methods The transcriptional data of GSVVs and normal great saphenous vein tissues(control tissues)were downloaded from the gene expression omnibus database.The single sample gene set enrichment analysis(ssGSEA)was used to calculate the Hallmark score.The weighted gene co-expression network analysis(WGCNA)combined with machine learning algorithms was used to screen the key genes relevant GSVVs.The protein-protein interaction(PPI)analysis was performed using the String database,and the receiver operating characteristic(ROC)curve was used to reflect the discrimination ability of the target genes for GSVVs.Results Compared with the control tissues,there were 548 upregulated genes and 706 down-regulated genes in the GSVVs tissues,the Hallmark points of KRAS signaling and apical junction were down-regulated,while which of peroxisomes,coagulation,reactive oxygen species pathways,etc.were upregulated in the GSVVs tissues.A total of 639 differentially expressed genes relevant GSVVs were obtained and 165 interaction relations between proteins encoded by 372 genes,and the top 10 genes with the highest betweeness values,ADAM10,APP,NCBP2,SP1,ASB6,ADCY4,HP,UBE2C,QSOX1,and CXCL1,were located at the center of the interaction relation.And the core genes were mainly related to copper ion homeostasis,neutrophil degranulation G protein coupled receptor signaling,response to oxidative stress,and regulation of amide metabolism processes.The SP1 and QSOX1 were both Hub genes.The expressions of the SP1 and QSOX1 in the GSVVs tissues were significantly up-regulated as compared with the control tissues.The areas under the ROC curves of SP1 and QSOX1 in distinguishing GSVVs tissues from normal tissues were 0.972 and 1.000,respectively.Conclusions SP1 and QSOX1 are core genes in the occurrence and development of GSVVs.Regulation of SP1 or QSOX1 gene is expected to achieve precise treatment of GSVVs.

关 键 词：大隐静脉曲张 生物信息学分析 核心基因 

分 类 号：R73[医药卫生—肿瘤]