口腔鳞状细胞癌患者预后相关基因标志物的生物信息学分析

Identification of potential genetic markers in prognosis of oral squamous cell carcinoma patients by bioinfor⁃matic analysis

目的通过生物信息分析方法筛选口腔鳞状细胞癌与癌旁组织之间的差异表达基因,初步确定潜在生物标志物。方法从基因表达数据库(Gene Expression Omnibus,GEO)中下载口腔鳞状细胞癌相关芯片数据集GSE23558、GSE37991、GSE30784,利用GEO在线分析工具筛选差异表达基因,并对其进行基因本体、京都基因与基因组百科全书分析。利用STRING在线数据库,构建差异基因蛋白互作(protein⁃protein interaction,PPI)网络,并通过Cytoscape筛选关键基因。进而使用Kaplan Meier在线软件对差异表达基因进行预后分析,并使用GEPIA(http://gepia.cancer⁃pku.cn/)验证其表达情况。结果共筛选出212个差异表达基因,进一步分析发现16个核心基因,其中与预后相关的核心基因包括:极光激酶A(aurora kinase A,AURKA)、极光激酶B(aurora kinase B,AURKB)、细胞凋亡抑制因子5(baculoviral IAP repeat containing 5,BIRC5)、细胞分裂周期蛋白6(cell division cycle 6,CDC6)、E2F转录因子7(E2F transcription factor 7,E2F7)、泛素样含PHD和环指域蛋白1(ubiquitin⁃like with PHD and ring finger domains 1,UHRF1),这些关键基因与癌旁组织相比在口腔鳞状细胞癌组织呈高表达并且患者生存时间均较短,差异均具有统计学意义(P<0.05)。结论AURKA、AURKB、BIRC5、CDC6、E2F7和UHRF1可作为口腔鳞状细胞癌患者预后潜在的标志物。

Objective To analyze the differentially expressed genes of patients with oral squamous cell carcinoma(OSCC) from paracarcinoma through biological information analysis to preliminarily identify OSCC⁃associated genes.Methods GSE23558, GSE37991 and GSE30784 were downloaded from the Gene Expression Omnibus (GEO), whichis the mRNA expression profile dataset. The differentially expressed genes (DEGs) were identified based on the gene on⁃tology and the Kyoto Encyclopedia of Genes and Genomes. Then, the protein⁃protein interaction (PPI) network was con⁃structed using the STRING online tool, and Cytoscape was used to filter the critical genes. Furthermore, key genes in⁃volved in the survival of patients with OSCC were analyzed using Kaplan⁃Meier analysis. The expression of hub geneswas validated based on GEPIA(http://gepia.cancer⁃pku.cn/). Results A total of 212 DEGs were screened, and further analysis revealed 16 core genes, among which the core genes associated with prognosis included aurora kinase A(AURKA), aurora kinase B (AURKB), apoptosis inhibiting factor 5 (BIRC5), cell division cycle 6 (CDC6), E2F transcrip⁃tion factor 7 (E2F7), ubiquitin⁃like with PHD and ring finger domains 1 (UHRF1). These key genes were highly ex⁃pressed in patients with oral squamous cell carcinoma, and the survival time of patients was short;the difference wasstatistically significant (P < 0.05). Conclusion AURKA, AURKB, BIRC5, CDC6, E2F7 and UHRF1 may be useful aspotential biomarkers for OSCC prognosis prediction.