头颈部鳞癌程序性死亡配体-1的共表达基因及调控网络的生物信息学分析
Bioinformatics analysis of programmed cell death ligand 1 co-expression genes and their regulatory network in head and neck squamous cell carcinoma
作者：杨利洒,石从郁,梁宇豪,刘曈,侯笑茹,田旭东,王晓毅
Author：Yang Lisa,Shi Congyu,Liang Yuhao,Liu Tong,Hou Xiaoru,Tian Xudong,Wang Xiaoyi
收稿日期： 年卷（期）页码：2019,37(5):516-516-520
期刊名称：华西口腔医学杂志
Journal Name：West China Journal of Stomatology
关键字：头颈部鳞癌,生物信息学,程序性死亡配体-1,程序性死亡受体-1,
Key words：head and neck squamous cell carcinoma,bioinformatics analysis,programmed cell death ligand 1,programmed cell death protein 1,
基金项目：
中文摘要
目的 运用生物信息学的方法绘制头颈部鳞癌（HNSCC）中程序性死亡配体-1（PD-L1）共表达基因关系网络,筛选潜在的PD-L1的协同标志物,寻找可能的PD-L1基因调控肿瘤免疫状态的基因和通路。方法 利用癌症和肿瘤基因图谱（TCGA）中的大样本HNSCC的转录组学数据,在cBioPortal数据平台进行基因集的检索,筛选PD-L1共表达基因,在R语言的clusterProfiler中进行GO-BP和KEGG富集分析,再进行分子关系网络分析,提取重要节点基因（hub基因）,再进行生存分析。结果 筛选出共表达基因117个,共表达基因主要富集在免疫调节和病毒反应过程。网络节度分析得到了10个hub基因,依次为STAT1、IFNG、CXCL10、CCR5、FCGR3A、CXCL9、GBP5、CD86、GZMB、IRF1。生存分析显示：CCR5、CXCL9、GZMB是HNSCC预后相关的重要基因。这些基因均参与了免疫过程,其表达与PD-L1相关（Pearson相关系数为0.30、0.35、0.39,P值均小于0.01）。这些基因高表达在HNSCC中均为保护因素。结论 HNSCC中的PD-L1共表达的主要基因均为免疫相关基因,其中CCR5、CXCL9、GZMB与PD-L1存在共表达关系,与预后相关,其可能与程序性死亡受体-1（PD-1）/PD-L1介导的肿瘤免疫逃避相关,为进一步研究PD-1/PD-L1的作用机制和精准靶向治疗提供了新的参考。
英文摘要
ObjectiveThis study aimed to construct a network of programmed celldeath ligand 1 (PD-L1) co-expression genes and screen potential biomarkers for PD-L1 expression in head and neck squamous cell carcinoma (HNSCC) by bioinformatics analysis. Moreover, the genes and pathways participating in PD-L1 and regulating the tumor immune status were determined.MethodsThe HNSCC transcriptomic dataset in TCGA was selected to retrieve gene sets on the cBioPortal platform, where PD-L1 co-expressional genes were acquired. With these genes, GO-BP, KEGG, and string analyses were performed in R clusterProfiler. Cytoscape was used for network analysis and hub gene screening.ResultsA total of 117 co-expression genes were obtained, most of which were enriched in immune regulation and response to viral processes. Node degree analysis indicated that STAT1, IFNG, CXCL10, CCR5, FCGR3A, CXCL9, GBP5, CD86, GZMB, IRF1 were the highest connected genes and functioned as hub genes. Survival analysis of these hub genes resulted in CCR5, CXCL9, and GZMB as the prognostic biomarkers for patients with HNSCC, all of which were involved in immune regulation and their expression levels were related to PD-L1 (Pearson correlation coefficient was 0.30, 0.35, 0.39;PConclusionPD-L1 co-expression hub genes are related to immunity, among which CCR5, CXCL9, and GZMB are prognostic markers with the possibility to be involved in programmed cell death protein 1 (PD-1)/PD-L1-induced tumor immune escape. These genes provide new clues to study the mechanism and precision target medicine of PD-1/PD-L1 in HNSCC.
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