李明,段世博,候秀真,张荣菊,党万里,郑新英,金燕.PI3K在妊娠期糖尿病发病机制中的作用生物信息分析及验证[J].转化医学杂志,2020,9(5):271-275
PI3K在妊娠期糖尿病发病机制中的作用生物信息分析及验证
Bioinformatics analysis and verification of PI3K in the pathogenesis of gestational diabetes mellitus
  
DOI:
中文关键词:  妊娠糖尿病  磷脂酰肌醇3-激酶  生物信息学分析
英文关键词:Gestational diabetes mellitus (GDM)  Phosphatidylinositide3-kinase (PI3K)  Bioinformatics analysis
基金项目:沧州市科技计划项目资助(162302031)
作者单位
李明 沧州市中心医院妇产科 
段世博 沧州市中心医院神经外科 
候秀真 沧州市中心医院妇产科 
张荣菊 沧州市中心医院病理科 
党万里 沧州市中心医院病理科 
郑新英 沧州市中心医院妇产科 
金燕 沧州市中心医院妇产科 
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中文摘要:
      目的利用大数据生物信息挖掘算法探讨妊娠期糖尿病(gestational diabetes mellitus,GDM)发病相关基因及其可能生物学功能在GDM发病机制中的作用。方法首先检索基因表达数据库,筛选并下载GDM差异表达芯片数据,采用R软件Lima包对差异表达基因进行筛选(Log2FC>1;P<0.05);对筛选出的差异表达基因进行功能富集分析。采用数据库STRING构建GDM发病机制蛋白-蛋白相互作用网络,分析差异表达基因编码蛋白间的相互作用关系。利用Cytohubb软件进一步筛选信号通路中关键基因(hub基因);同时选取30例GDM患者和30名正常分娩孕妇为研究对象,采用免疫组化方法对关键基因编码蛋白在GDM患者胎盘组织及正常妊娠产妇胎盘组织中的表达水平进行检测。结果2个数据集GSE51546和GSE87295纳入本次分析,2个数据集中共差异表达基因4个[TACSTD2,磷脂酰肌醇3-激酶(phosphatidylinositide 3-kinase,PI3K),COLEC12和IGFBP6]。差异表达基因蛋白主要位于细胞质和细胞接合器,主要分子功能为磷酸转移酶活性,醇基作为受体和蛋白激酶,主要参与体内相关蛋白信号转导。京都基因百科全书通路分析显示,差异基因主要参与了PI3K-Akt信号通路、糖代谢途径相关通路和胰岛素信号通路。与筛选出的4个差异表达基因编码蛋白-蛋白相互作用网络54个蛋白节点,共574个相互作用链接,平均连接度为21.3,聚集度为0.74。根据蛋白-蛋白相互作用网络筛选出PI3K、TAL1和LYL1为GDM差异表达蛋白-蛋白网络中的关键基因(hub基因),其中PI3K在3个关键基因中作用最为重要。GDM组中,阳性表达率为70.0%(21/30),正常妊娠组阳性表达率达为100%(30/30)。GDM患者胎盘组织中PI3K的阳性表达低于正常妊娠者,差异有统计学意义(χ2=22.47,P<0.05)。结论PI3K在GDM患者中存在明显的差异表达,并可能在GDM发生、发展中发挥重要作用。PI3K可能成为治疗和预防GDM的关键靶点。
英文摘要:
      Objective To explore the pathogenesis of gestational diabetic nephropathy (GDM) and its possible biological functions by using large data bioinformatics mining algorithm. Methods The Gene Expression Omnibus(GEO) was retrieved and the data of GDM differential expression chip were screened and downloaded. The differentially expressed genes were screened by using R software Lima package (Log2FC>1; P<0.05). Functional enrichment of differentially expressed genes was performed. The protein-protein interaction network of GDM pathogenesis was constructed using the database (STRING) to analyze the interaction between differentially expressed gene-coding proteins. Cytohubb software was used to further screen the key genes (hub genes) in the signaling pathway. At the same time, 30 cases of GDM and 30 normal pregnant women were selected as subjects. The expression levels of key gene coding proteins in placenta tissues of GDM patients and normal pregnant women were detected by immunohistochemical method. ResultsTwo datasets GSE51546 and GSE87295 were included in this analysis. There were four differentially expressed genes [TACSTD2,phosphatidylinositide 3-kinase(PI3K), COLEC12 and IGFBP6] in the two datasets. Differentially expressed gene products are mainly located in cytoplasm and cell conjugator. The main molecular function is phosphatase activity. Alcohol groups are receptors and protein kinases, which are mainly involved in the signal transduction of related proteins in vivo. KEGG pathway analysis showed that the differentially expressed genes were mainly involved in PI3K-Akt signaling pathway, glucose metabolism pathway and insulin signaling pathway. There were 54 protein nodes and 574 interaction links in the protein-protein interaction network with four differentially expressed genes. The average connectivity and aggregation were 21.3 and 0.74, respectively. According to protein-protein interaction network, PI3K, TAL1 and LYL1 were selected as the related genes in the differential expression protein-protein network of GDM, among which PI3K played the most important role in the three key genes. The positive expression rate of the GDM group was 70.0% (21/30). But, in normal pregnancy group, the positive expression rate was 100% (30/30). The positive expression of PI3K in placenta of GDM patients was lower than that of normal pregnant women (χ2=22.47, P< 0.05). ConclusionPI3K is differentially expressed in patients with GDM and may play an important role in the occurrence and development of GDM. PI3K may be a key target for the treatment and prevention of GDM.
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