摘要
目的通过基因表达综合(GEO)数据库对进行性核上性麻痹(PSP)相关基因芯片进行生物信息学分析,获得PSP的生物标志物及其调控的关键通路。方法从GEO2R分析工具获取PSP相关基因芯片的基因表达数据集GSE6613,筛选出差异表达基因(DEGs),并借助DAVID在线分析平台对这些基因进行基因本体论(GO)富集分析和京都基因与基因组百科全书(KEGG)信号通路分析。利用生物信息学软件STRING构建这些基因的蛋白-蛋白相互作用(PPI)网络,找出连接度最高的核心基因。临床标本验证:选取2016年1月至2021年12月收治的9例PSP患者作为试验组,选取2022年1月至2022年2月行常规查体的非PSP患者作为对照组,留取上述人群血液标本并提取总RNA,实时荧光定量PCR检测生物信息学分析得出的DEGs及PPI网络中的核心基因表达水平。结果该研究中所采用的GSE6613数据集共包含6例PSP患者及23例健康者。共筛选出DEGs 98个,包括52个上调基因及46个下调基因。其中,差异最大的5个上调基因依次为MYOM2、EMP1、DKK2、FBN1、POLA2;差异最大的5个下调基因依次IVD、TMED7、MSMO1、CASP3和DLG1。GO和KEGG结果表明,PSP发展过程中的DEGs主要富集在炎症、免疫紊乱、代谢紊乱等方面。PPI网络揭示连接度最高的核心基因为KRAS。临床标本验证显示,与对照组比较,试验组EMP1和DKK2基因表达上调,DLG1和KRAS基因表达下调,差异均有统计学意义(P<0.05)。结论PSP患者的DEGs与炎症、免疫紊乱及能量代谢密切相关,EMP1、DKK2和DLG1基因有望成为PSP诊断的分子标志物,核心基因KRAS有望成为PSP潜在治疗靶点。
Objective To obtain biomarkers of progressive supranuclear palsy(PSP)and the key passages of its regulation through bioinformatic analysis of gene microarrays associated with PSP in the Gene Expression Omnibus(GEO)database.Methods Gene expression microarrays(GSE6613)of PSP were obtained from the GEO2R database to screen out differentially expressed genes(DEGs)and these genes were subjected to gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway analysis with the help of the DAVID online analysis platform.The protein-protein interaction(PPI)network of these genes was constructed using the bioinformatics software STRING to identify the core genes with the highest connectivity.Clinical specimen validation:9 PSP patients admitted from January 2016 to December 2021 were enrolled as the experimental group,and non-PSP patients who performed routine checkups from January 2022 to February 2022 were ennrolled as the control group,blood specimens were retained and total RNA was extracted,the expression levels of differentially expressed genes and core genes in the PPI network derived from bioinformatics analysis were detected by real-time quantitative PCR.Results The microarray GSE6613 used in this study included 6 PSP patients and 23 healthy people.A total of 98 differentially expressed genes(DEGs)were found,including 52 up-regulated genes and 46 down-regulated genes.Among them,the five most differentially up-regulated genes were MYOM2,EMP1,DKK2,FBN1,and POLA2 in order;the five most differentially down-regulated genes were IVD,TMED7,MSMO1,CASP3,and DLG1 in order.The GO and KEGG results indicated that DEGs during PSP development were mainly enriched in inflammation,immune disorders,and metabolic disorders.The PPI network revealed that the most highly connected core gene was KRAS.Clinical specimen validation showed that EMP1 and DKK2 gene expression was upregulated and DLG1 and KRAS gene expression was downregulated in the experimental group compared to the control group,wit
作者
王婵娟
郝志敏
张伟兰
熊三军
郭美祥
WANG Chanjuan;HAO Zhimin;ZHANG Weilan;XIONG Sanjun;GUO Meixiang(Department of General Medicine,Fengxian District Central Hospital,Shanghai 201400,China)
出处
《检验医学与临床》
CAS
2022年第20期2786-2790,共5页
Laboratory Medicine and Clinic
基金
上海市奉贤区科技发展基金项目(20201428)。
