HCST作为1型糖尿病潜在分子标志物的筛选和机制探究

Screening and mechanism exploration of HCST as a potential biomarker in type 1 diabetes mellitus

目的:筛选1型糖尿病(T1DM)的潜在分子标志物并分析HCST参与T1DM的可能机制。方法:从GEO数据库下载T1DM和健康人群的单个核细胞微阵列表达数据,借助GEO2R分析差异基因,同时使用R语言进行火山图和热图的可视化。利用String在线工具对差异基因进行PPI分析,MCODE插件筛选关键子网络,DAVID在线分析工具对子网络基因进行GO和KEGG富集分析;CytoHubba插件对PPI网络进行关键基因筛选。结果:T1DM组与对照组相比共得到71个差异基因,其中包含上调基因22个,下调基因49个;利用MCODE插件从PPI网络中筛选1个关键子网络,得分7.5,共有9个节点和30个互作。子网络的9个基因的GO和KEGG富集分析发现,这9个基因主要参与调节免疫反应、细胞的防御反应、免疫应答及细胞溶解的生物过程,且涉及的主要信号通路是自然杀伤细胞介导的细胞毒作用的信号通路;四种算法得到的关键基因通过Venn分析最终筛选出1个关键基因——HCST。HCST在T1DM组明显低于健康对照组,差异有统计学意义。HCST的ROC曲线分析结果显示曲线下面积为0.983 3,P=0.000 1,差异有统计学意义。结论:HCST可成为诊断T1DM的潜在分子标志物和治疗T1DM的潜在靶点。

Objective:To screen potential molecular markers of type 1 diabetes mellitus(T1DM)and analyze the possible mechanism of HCST involved in T1DM.Methods:Microarray expression data of mononuclear cells from T1DM and healthy people were downloaded from GEO database,differential genes were analyzed with the help of GEO2R,and volcano map and heat map were visualized using R language at the same time.PPI analysis of differential genes was performed using String online tool,key subnetworks were screened by MCODE plugin,GO and KEGG enrichment analysis of subnetwork genes were performed with the help of DAVID online analysis tool;PPI networks screened for key genes using CytoHubba plugin.Results:A total of 71 differential genes were obtained in T1DM group compared with control group,of which 22 were up-regulated and 49 were down-regulated;one key subnetwork was screened from the PPI network using MCODE plugin,with a score of 7.5,a total of 9 nodes and 30 interactions.GO and KEGG enrichment analysis of the nine genes of subnetwork revealed that these nine genes were mainly involved in regulating immune responses,cellular defense responses,biological processes involved in immune responses and cytolysis,and that the main signaling pathways involved were signaling pathways of natural killer cell-mediated cytotoxicity;key genes obtained by the four algorithms were finally selected as one key gene of HCST by Venn analysis.HCST was significantly lower in T1DM group than in healthy control group,and the difference was statistically significant.Results of ROC curve analysis of HCST showed that the area under the curve was 0.9833,P=0.0001,and the difference was statistically significant.Conclusion:HCST may be a potential molecular marker for diagnosis of T1DM and a potential target for treatment of T1DM.