解放军医学杂志2017，Vol.42Issue(5)：361-365,5.DOI:10.11855/j.issn.0577-7402.2017.05.01
肺鳞癌PD-L1共表达基因及转录调控网络分析
Co-expression and transcriptional regulation network analysis of PD-L1 in lung squamous cell carcinoma
摘要
Abstract
Objective To construct a programmed cell death ligand 1(PD-L1) co-expression network in lung squamous cell carcinoma,screen potential PD-L1 co-expression biomarkers,and try to find the genes and pathways participating in PD-L1-regulated tumor immune response.Methods The lung squamous cell carcinoma dataset extracted from TCGA was used to screen the co-expression genes of PD-L 1 at the whole-genome transcriptional level by Venny analysis,and the target genes were screened by multiple types of cluster and molecular network analysis to construct a PD-L1 co-expression network.Results A total of 126 genes moderately co-expressed with PD-L1 were retrieved,most of them are plasma membrane targeting genes participating in immune response.Three transcription factors (IRF2/NFKB1/IRF1) were involved in more than 30％ the regulation of the PD-L1 genes transcription.By screening the core molecules of co-expression of PD-L1 gene set and analyzing the connectivity of network node,6 network nodes genes with the highest connectivity were retrieved as follows:IFNG,JAK2,STAT1,CTLA4,CD80 and CCR5.Analysis of the relations of the different expression levels of these genes to the survival situation of patients with lung cancer revealed that CCR5 was a significant prognostic marker.Analysis of the PD-L1 expression and CCR5 gene spectrum data showed the Pearson correlation coefficient is 0.47(P＜0.05);GO-BP cluster analysis showed that the function of CCR5 mainly focused on immune regulation,T cell regulation and signal transduction,in accordance with the PD-L1 function of network regulation.Conclusions The main nodes of PD-L1 co-expressing gene set are immune-related molecules,among which IFNG/CCR5/NFKB1 play the most significant regulatory effects in the gene network.This finding lays a foundation for the research and immunotherapy for lung squamous cell carcinoma.关键词
肺肿癌/癌,鳞状细胞/细胞程序性死亡配体1/免疫调控Key words
lung neoplasms/carcinoma,squamous cell/programmed cell death ligand 1/immune regulation分类
医药卫生引用本文复制引用
冯飞跃,邱斌,李春晓,钱海利,高树庚..肺鳞癌PD-L1共表达基因及转录调控网络分析[J].解放军医学杂志,2017,42(5):361-365,5.基金项目
国家重点研发计划项目(2016YFC0905400)This work was supported by the National Key Research and Development Program (2016YFC0905400) （2016YFC0905400）
