肺鳞癌PD-L1共表达基因及转录调控网络分析

发布时间：2018-06-26 22:17

本文选题：肺肿癌 + 癌　；参考：《解放军医学杂志》2017年05期

【摘要】：目的绘制肺鳞癌中细胞程序性死亡配体1(PD-L1)共表达基因关系网络,筛选潜在的PD-L1协同检测生物标志物,寻找可能参与PD-L1调控肿瘤免疫状态的基因及通路。方法采用TCGA肺鳞癌数据集,利用c Bio Portal数据分析平台进行共表达基因集检索,从全基因转录组水平对PD-L1的共表达基因进行Venny分析,筛选目标基因,进行多种类型的聚类和分子关系网络分析,并建立PD-L1调控网络。结果共获得PD-L1中等程度表达相关基因126个,主要为质膜定位型基因,功能集中在免疫调节过程,其中IRF2/NFKB1/IRF1三个转录因子参与了对PD-L1基因集30%以上基因的转录调控。经过PD-L1共表达基因集的核心分子筛选,分析网络节点连接度,得到具有最高连接度的前6个节点基因,依次为IFNG、JAK2、STAT1、CTLA4、CD80和CCR5,对这些基因不同表达水平的肺癌患者的生存情况进行分析,结果显示CCR5是一个有意义的预后指标分子。进一步对PD-L1和CCR5的表达谱数据进行相关性分析,结果显示CCR5与PD-L1表达谱水平的Pearson相关系数为0.47(P0.05);GO-BP聚类分析显示,CCR5的功能主要聚集在免疫调控、T细胞调控、细胞信号转导等领域,与PD-L1调控网络的功能相符。结论 PD-L1共表达基因集内的主要节点均为免疫相关分子,其中IFNG、CCR5、NFKB1分子对PD-L1共表达基因网络具有最广泛的调控作用,该发现为肺鳞癌免疫治疗的研究和应用奠定了一定基础。
[Abstract]:Objective to map the coexpression network of programmed cell death ligand 1 (PD-L1) in lung squamous cell carcinoma, screening potential PD-L1 CO detection biomarkers and searching for genes and pathways that may participate in the regulation of tumor immune state by PD-L1. Methods using the data set of TCGA lung squamous cell carcinoma and using C Bio Portal data analysis platform for co expression gene collection detection. Venny analysis of CO expressed genes of PD-L1 from all gene transcriptome levels, screening target genes, conducting a variety of types of clustering and molecular relationship network analysis, and establishing a PD-L1 regulatory network. The results obtained a total of 126 related genes expressed in the middle degree of PD-L1, mainly the membrane location-type gene, and the function concentrated in the immunomodulatory process. IRF2/NFKB1/IRF1 three transcription factors participated in the transcriptional regulation of more than 30% genes of the PD-L1 gene set. Through the screening of the core molecules of the PD-L1 co expression gene set, the connectivity of the network nodes was analyzed, and the top 6 node genes with the highest connectivity were obtained, which were respectively IFNG, JAK2, STAT1, CTLA4, CD80 and CCR5. The survival of the patients with lung cancer was analyzed. The results showed that CCR5 was a meaningful prognostic indicator. Further correlation analysis of the expression profiles of PD-L1 and CCR5 showed that the Pearson correlation coefficient of CCR5 and PD-L1 expression profiles was 0.47 (P0.05); GO-BP clustering analysis showed that the function of CCR5 was mainly concentrated in the exemption. The regulation of pestilence, T cell regulation, cell signal transduction, and other fields are consistent with the functions of the PD-L1 regulatory network. Conclusion the main nodes in the PD-L1 co expressed gene set are all immune related molecules, in which IFNG, CCR5, and NFKB1 molecules have the most extensive regulation for the PD-L1 co expression gene network. This discovery is the research and application of the immunotherapy of lung squamous cell carcinoma. A certain foundation has been laid.
【作者单位】：国家癌症中心/中国医学科学院北京协和医学院肿瘤医院胸外科;国家癌症中心/中国医学科学院北京协和医学院分子肿瘤学国家重点实验室;
【基金】：国家重点研发计划项目(2016YFC0905400)~~
【分类号】：R734.2

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