通过生物信息学筛选头颈部鳞状细胞癌差异表达基因及相关生物学特性分析  

Screening of differentially expressed genes and related biological characteristics of head and neck squamous cell carcinoma by bioinformatics

作　　者：王凯[1] 肖剑 宋业勋[1] 李和清[1] WANG Kai;XIAO Jian;SONG Yexun;LI Heqing(Department of Otolaryngology Head and Neck Surgery,the Third Xiangya Hospital of Central South University,Changsha,Hunan,410000,China)

机构地区：[1]中南大学湘雅三医院耳鼻咽喉头颈外科,湖南长沙410000

出　　处：《中国耳鼻咽喉头颈外科》2020年第7期377-381,共5页Chinese Archives of Otolaryngology-Head and Neck Surgery

基　　金：国家自然科学基金资助项目(81702706)。

摘　　要：目的利用生物信息学方法,筛选出与头颈鳞状细胞癌发生发展相关的差异表达基因(differentially expressed genes,DEGs),进而寻找出有助于头颈鳞状细胞癌早期诊断和预后的分子生物标志物。方法整合3个GEO数据库,筛选DEGs,进行GO(gene ontology)功能注释及KEGG(the Kyoto Encyclopedia of Gene and Genomes)通路富集分析,构建蛋白质-蛋白质作用网络(protein-protein interaction,PPI),提取关键基因,验证其差异表达水平及与预后的关系。结果从数据集中共筛选出39个上调基因和44个下调基因;GO分析发现上调的DEGs生物学功能主要是细胞外基质结构活性、结构分子活性等,下调的DEGs主要与代谢、结构分子活性等有关。KEGG分析表明上调的DEGs主要在PI3k-Akt信号通路、粘着斑;下调的DEGs主要集中在化学致癌、药物代谢-细胞色素P450途径。通过PPI筛选出4个关键基因MMP1、PLAU、RBP1、SEMA3C与头颈鳞状细胞癌的无病生存期显著相关,且高表达组的预后显著差于低表达组。结论本研究筛选出MMP1、PLAU、RBP1、SEMA3C与头颈鳞状细胞癌的发生发展和预后相关,为临床诊断和治疗提供了新的靶点。OBJECTIVE To screen differentially expressed genes(DEGs)which are related with the development of head and neck squamous cell carcinoma(HNSCC)in the bioinformatical way.Moreover,results from the study might make the tumorigenesis of head and neck clear and bring the biomarkers for early diagnosis and predictions.METHODS To select DEGs,we should integrate the whole gene expression profile data of three GEO databases.Through gene ontology(GO)analysis,the Kyoto Encyclopedia of Gene and Genomes(KEGG)analysis and protein-protein interaction(PPI)network building,we can obtain hug genes,and then confirming the relationship between the expression level of hug genes and prognosis of HNSCC.RESULTS Finally,we found out 39 up-regulated genes and 44 down-regulated genes coming from three data sets.GO analysis revealed that the major biological functions of the up-regulated DEGs were extracellular matrix structure and structural molecular activity.The down-regulated DEGs were connected with metabolism and structural molecular activity.KEGG analysis showed the up-regulated DEGs were mainly concentrated in the PI3k-Akt signaling pathway,and focal adhesions.Meanwhile,the down-regulated DEGs were among chemical carcinogenesis,drug metabolism-cytochrome P450,and metabolic pathways.Based on the construction of a protein-protein interaction network,we acquired the four hug genes MMP1,PLAU,RBP1,and SEMA3C.At last,the four hug genes were significantly correlated with disease-free survival of HNSCC,and the prognosis of the high expression group was significantly worse than that of the low expression group.CONCLUSION In this study,four hug genes were picked out.There are MMP1,PLAU,RBP1,and SEMA3C,which related to the development and prognosis of HNSCC,and it provide new targets for clinical diagnosis and treatment.

关 键 词：癌 鳞状细胞 预后 生物信息学 差异表达基因 生物标志物 

分 类 号：R739.91[医药卫生—肿瘤]