整合生物信息学鉴定宫颈高级别鳞状上皮内病变的关键基因

Integrating Bioinformatics to Identify Key Genes for Cervical High-Grade Squamous Intraepithelial Lesions

目的通过多芯片数据整合分析筛选高级别鳞状上皮内病变(HSIL)发生发展的关键基因,鉴定与HSIL密切相关的生物标志物及潜在的药物靶点。方法从GEO数据库下载HSIL的基因表达数据,并通过鲁棒秩聚合法(RRA)获得HSIL组和对照组(正常宫颈组织)之间的差异表达基因,随后进行基因功能注释和蛋白互作网络(PPI)分析,分析这些差异表达基因的生物学功能,鉴定与HSIL密切相关的关键基因。结果共纳入GSE63514、GSE7803、GSE138080和GSE26278四个数据集,共包含105个HSIL样品和56个正常宫颈组织样品。RRA集成分析确定了175个显著的差异表达基因(上调基因77个,下调基因98个),其中最显著上调的基因是细胞周期蛋白依赖性激酶抑制剂2A(CDKN2A),最显著下调的基因是富半胱氨酸的C端1(CRCT1)。根据PPI和RRA的结果,最终确定了5个与HSIL密切相关的关键基因,包括CXC趋化因子配体1(CXCL1)、胞嘧啶脱苷酶(CDA)、乳铁蛋白(LTF)、CDKN2A、CRCT1。结论CXCL1、CDA、LTF、CDKN2A、CRCT1可能作为HSIL的生物标志物,可能为HSIL的早期筛查和个体化治疗提供理论依据。

Objective To explore the key genes that have closely related to the occurrence and development of high-grades quamous intraepithelial lesion(HSIL)through multi-chip data integration analysis,and to identify new biomarkers and potential drug therapy targets for HSIL.Methods The gene expression data of HSIL were downloaded from GEO,and the differentially expressed gene,between the HSIL group and control group(normal cervical tissue)were obtained by robust rank aggretation(RRA).Then gene functional annotation and PPI analysis were performed to explore the potential function of these differentially expressed genes and identify the key genes closely related to HSIL.Results In this study,four data sets of GSE63514,GSE7803,GSE138080 and GSE26278 were included,which including 105 HSIL samples and 56 normal cervical tissue samples.RRA integrated analysis identified 175 significant differentially expressed genes(77 up-regulated genes and 98 down-regulated genes),from them,the most significant down-regulated gene was cyclin-dependent kinase inhibitor 2A(CDKN2A),and the most significant up-regulated gene was cysteine rich C-terminal 1(CRCT1).According to the results of PPI and RRA,we finally identified five key genes closely related to HSIL,including chemokine(C-X-C motif)ligand 1(CXCL1),cytidine deaminase(CDA),lactotransferrin(LTF),CDKN2A and CRCT1.Conclusion CXCL1,CDA,LTF,CDKN2A,CRCT1 may be used as biomarkers of HSIL,which may provide a theoretical basis for early screening and individualized treatment of HSIL.