摘要
为了探讨电离辐射对肿瘤相关成纤维细胞中基因表达的影响,我们从GEO数据库中检索获得电离辐射处理后的肿瘤相关成纤维细胞基因表达谱数据芯片GSE37318,利用GEO2R软件筛选差异表达基因;利用DAVID工具进行GO和KEGG途径富集分析;利用Cytoscape软件构建蛋白质相互作用网络并获取核心基因;利用GEPIA进行预后价值分析。结果共筛选获得上调表达基因144个,下调表达基因54个,主要富集在细胞应激、DNA损伤、细胞周期、衰老、细胞凋亡、氧化应激和p53信号通路等功能途径。构建了包含103个节点,376条边的蛋白质相互作用网络,获得了前20个枢纽基因。预后分析表明:MCM10、DLGAP5、FANCI、CENPA、CDC6、FBXO5、NCAPG和DTL等辐照后表达下调的枢纽基因,其表达水平均与肺癌患者的总生存时间呈负相关(p<0.05);PCNA等辐照后表达上调的枢纽基因,其表达水平也与肺癌患者的预后呈负相关(p<0.05)。结果提示,电离辐射处理能导致肿瘤相关成纤维细胞中部分基因表达上调,部分基因表达下调,这些差异表达基因为评估肿瘤放疗效果、病人预后以及复发转移风险提供了潜在的分子标记。
Tumor-associated fibroblast gene expression microarray data were obtained from the GEO database(GSE37318).Data were screened for differentially expressed genes using GEO2R software.GO and KEGG pathways were analyzed using the DAVID tool.A protein-protein interaction network was then constructed,and hub genes were identified using Cytoscape software.Prognostic value analysis of hub genes was performed using GEPIA.A total of 144 up-regulated genes and 54 down-regulated genes were identified from the dataset GSE37318.These were mainly expressed during cell stress,DNA damage,cell cycle,senescence,apoptosis,oxidative stress,and in the p53 signaling pathway.A protein-protein interaction network consisting of 103 nodes and 376 edges was constructed,and the top 20 hub genes were identified.Of the top 10 hub genes,low expression levels of eight genes including MCM10,DLGAP5,FANCI,CENPA,CDC6,FBXO5,NCAPG,and DTL were related to poor overall survival(OS)in lung cancer patients(p<0.05).However,high levels of PCNA expression were also associated with poor OS in lung cancer patients(p<0.05).Ionizing radiation may induce both up-and down-regulation of genes in tumor-associated fibroblasts.These differentially expressed genes provide potential molecular markers for evaluating the efficacy of tumor radiotherapy,patient prognosis,risk of recurrence,and metastasis.
作者
杨宇虹
李娜
YANG Yuhong;LI Na(Department of Basic Medicine,Yongzhou Vocational Technical College,Yongzhou 425100,China;Department of Pathology,the First Affiliated Hospital of Hunan University of Medicine,Huaihua 418000,China;Hunan Provincial Key Laboratory of Dong Medicine,Hunan University of Medicine,Huaihua 418000,China)
出处
《辐射研究与辐射工艺学报》
CAS
CSCD
2020年第1期32-41,共10页
Journal of Radiation Research and Radiation Processing
基金
湖南省自然科学基金项目(2019JJ50425)
湖南省科技厅项目(2018SK4006)
湖南省教育厅一般项目(18C1129)资助~~
关键词
电离辐射
肿瘤
成纤维细胞
差异表达
基因
生物信息学
Ionizing radiation
Tumor
Fibroblast
Differential expression
Gene
Bioinformatics
