摘要
目的:应用生物信息学技术对口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)基因芯片数据进行差异表达基因(differentially expressed genes,DEGs)筛选,进一步预测潜在靶点及预后基因.方法:利用基因表达综合数据库(gene expression omnibus,GEO)下载基因芯片数据集(GSE23558 和GSE138206),联合GEO2R工具在线分析OSCC与正常口腔黏膜组织的DEGs;并对其进行相关通路、蛋白质相互作用(protein-protein interaction,PPI)网络及关键网络节点分析,筛选前 25 个枢纽基因,通过多个外部数据库对其进行验证.应用Timer网站进一步分析枢纽基因与免疫细胞浸润及免疫检查点的关系,基于Lasso-Cox算法,构建相关基因的预后风险模型.构建包含预后风险模型和多个临床病理因素的列线图.结果:分泌磷酸蛋白1(secreted phosphoprotein 1,SPP1)、整合素α3(integrin α3,ITGA3)基因在头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)中的表达水平与患者的不良预后相关(P<0.05).ITGA3被认为是具有未来临床意义的潜在免疫治疗靶点.基于SPP1和ITGA3基因构建的预后模型,可以有效预测OSCC患者的预后.结论:ITGA3、SPP1 可能为OSCC患者的治疗靶点及预后的生物标志物,并为探索OSCC的分子机制提供了理论依据.
Abstract
Objective:To apply bioinformatics technology to screen differentially expressed genes(DEGs)in oral squamous cell carcinoma(OSCC)microarray data to further predict potential targets and prognostic genes.Methods:GSE23558 and GSE138206 datasets were downloaded from gene expression omnibus(GEO)database to analyze DEGs of OSCC and normal oral mucosa tissues online with the help of GEO2R;the associated pathways,protein-protein interaction(PPI)network and key network nodes were analyzed,and the top 25 hub genes were screened and verified through multiple external databases.The Timer website was used to analyze the relationship between hub genes and immune cell infiltration and immune checkpoints.Based on Lasso-Cox algorithm,a prognostic risk model of related genes was constructed.A nomogram containing prognostic risk model and multiple clinicopathological factors was constructed.Results:Integrin α3(ITGA3)and secreted phosphoprotein 1(SPP1)genes were highly expressed in head and neck squamous cell carcinoma(HNSCC)tissues and were correlated with poor prognosis of patients(P<0.05).ITGA3 was considered to be a potential immunotherapy target with future clinical significance.The prognostic model based on SPP1 and ITGA3 genes can effectively predict the prognosis of OSCC patients.Conclusion:ITGA3 and SPP1 may be biomarkers for the prognosis of OSCC patients.These results provide new clues for exploring the molecular mechanism and targeted therapy of OSCC.
国家科技期刊平台
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