基于基因表达谱数据库的睾丸精原细胞瘤生物信息学分析

Bioinformatics analysis of testicular seminoma based on gene expression omnibus database

目的:利用生物信息学方法分析睾丸精原细胞瘤表达谱,筛选分析睾丸精原细胞相关基因。方法:睾丸精原细胞瘤相关数据来自基因表达谱(GEO)公共数据库(GSE8607、GSE1818),利用GEO2R程序筛选差异表达基因,取P<0.05,|Log2FC|>2的基因;利用在线程序String及Cytoscape软件的cytoHubba插件获取前10个关键基因,通过GEPIA在线工具对这些基因进行GO富集分析、揭示这些基因与病理分期相关性、明确这些基因在正常与肿瘤组织表达差异分析等。结果:2个芯片数据集差异分析交集获取差异基因255个,其中上调基因70个,下调基因185个。cytoHubba插件筛选出的前10个关键基因[细胞周期蛋白依赖性蛋白激酶4(CDK4)、细胞周期调节蛋白A1(CCNA1)、细胞周期蛋白依赖性蛋白激酶抑制剂2D(CDKN2D)、细胞周期调节蛋白D2(CCND2)、细胞周期调节蛋白O(CCNO)、细胞周期调节蛋白H(CCNH)、白细胞免疫球蛋白样受体2(LILRB2)、粒溶酶A(GZMA)、酪氨酸蛋白磷酸酶受体C(PTPRC)、主要组织相容性复合体的Ⅱ类抗原呈递分子(HLA-DRA)]。富集分析提示10个关键基因参与细胞分裂、有丝分裂周期调控、免疫应答、蛋白结合、丝氨酸/苏氨酸激酶调节活性等过程。核心基因与病理分期的相关性分析提示了4个基因[CCNA1(F=3.52,Pr(>F)=0.036)、CNCCD2(F=4.86,Pr(>F)=0.009)、PTPRC(F=4.45,Pr(>F)=0.014)、GZMA(F=3.24,Pr(>F)=0.042)]在病理分期方面有统计学差异。核心基因在肿瘤和正常睾丸组织中表达分析证实这些基因在肿瘤和正常睾丸组织中的差异性表达,其中CDK4、CCND2、LILRB2、GZMA、PTPRC、HLA-DRA在肿瘤组的表达量大于正常组(P<0.05)。结论:睾丸精原细胞瘤发生发展存在复杂的调控网络,生物信息学分析可以筛选出一些重要信息,为进一步研究睾丸精原细胞分子机制提供依据。

Objective To analyze the gene expression profile of testicular seminoma by bioinformatics,to screen the genes related to testicular seminoma and explore potential therapeutic targets.Methods The data of Testicular seminoma data were obtained from gene expression omnibus(GEO)public database(GSE8607,GSE1818).GEO2R was used to screen differentially expressed genes,and collect the target genes with P<0.05,|Log2 fold change|>2.String and cytoHubba were used to analyze related genes of the top 10.GEPIA online analysis tool was used to analyze GO,to reveal the correlation between these genes and pathological stage,and to identify the differences in the expression of these genes in normal and tumor tissues.Results A total of 255 differentially expressed genes were obtained from 2 databases,including 70 up-regulated genes and 185 down-regulated genes.The top 10 key genes were cyclin-dependent protein kinase 4(CDK4),cyclin A1(CCNA1),cyclin-dependent kinase inhibitor 2D(CDKN2D),cyclin D2(CCND2),cyclin O(CCNO),cyclin H(CCNH),leukocyte immunoglobulin-like receptor 2(LILRB2),granzyme A(GZMA),protein tyrosine phosphatase receptor type C(PTPRC),major histocompatibility complex,classⅡ,DR alpha(HLA-DRA).Enrichment analysis found that these genes were involved in cell division,mitotic cycle regulation,immune response,protein binding,and serine/threonine kinase regulation activity.Correlation analysis between core genes and pathological stage indicated that the four genes[CCNA1(F=3.52,Pr(>F)=0.036),CNCCD2(F=4.86,Pr(>F)=0.009),PTPRC(F=4.45,Pr(>F)=0.014),GZMA(F=3.24,Pr(>F)=0.042)]have statistical differences in pathological stage.Analysis of core gene expression in tumor and normal testicular tissue confirmed the differential expression of these genes in tumor and normal testicular tissues.The expression levels of CDK4,CCND2,LILRB2,GZMA,PTPRC and HLA-DRA in tumor group were higher than those in normal group(P<0.05).Conclusion There are complex regulatory networks in the occurrence and development of testicular seminoma.Bioinformatics analysis can screen out some important information and provide ideas for further research on the molecular mechanism of testicular spermatogonia.