摘要
目的通过生物信息学方法筛选和分析卵巢子宫内膜样癌差异表达的免疫相关基因,为研究卵巢子宫内膜样癌发病机制、早期诊断和预后判断提供参考。方法从高通量基因表达(GEO)数据库中选取微阵列转录基因数据集GSE57545,通过GEO在线分析工具GEO2R筛选出差异表达基因;使用标注、可视化和集成发现数据库(DAVID)对差异表达基因进行基因本体(GO)分析,京都基因与基因组百科全书(KEGG)通路分析;通过STRING数据库构建蛋白互作(PPI)网络,用Cytoscape获取10个具有高度连接性的关键基因;使用路径视图(pathview)进一步研究关键基因在通路中的表达和发挥作用的途径,并用Kaplan-Meier绘图仪分析关键基因表达患者的生存情况。结果通过对正常子宫内膜和卵巢子宫内膜样癌差异表达的免疫相关基因进行筛选获得87个差异表达基因,主要涉及免疫反应、炎症反应等通路。PPI网络和Cytoscape软件筛选出的10个关键基因,包括细胞黏附分子1(ICAM1)、Toll样受体2(TLR2)、C-X-C基序趋化因子配体8(CXCL8)、甘油醛-3-磷酸盐脱氢酶(GAPDH)、C-X-C基序趋化因子配体10(CXCL10)、IL-18、C-X-C基序趋化因子配体1(CXCL1)、C-X-C基序趋化因子配体2(CXCL2)、C-X-C基序趋化因子配体12(CXCL12)、前列腺素-内啡肽合成酶2(PTGS2)。pathview研究发现关键基因在吞噬体、Toll样受体信号通路、抗原处理和呈递通路中表达和发挥作用。生存分析表明TLR2、CXCL10、CXCL12、IL-18高表达和CXCL8、GAPDH、CXCL1低表达与卵巢子宫内膜样癌患者的无病生存和整体生存状况较差相关。结论卵巢子宫内膜样癌差异表达的免疫相关基因可能主要通过调控炎症反应和免疫应答,形成可以逃逸免疫的肿瘤微环境,引起卵巢子宫内膜样癌的发生、发展。
Objective To screen the differentially expressed immune-related genes in endometrioid ovarian cancer and their functional enrichment pathways.Methods The gene dataset GSE57545 was obtained from gene expression omnibus(GEO)database,and differentially expressed genes(DEGs)were screened by GEO2R.GO function and KEGG pathway analyses of DEGs were performed using DAVID database.The protein-protein interaction(PPI)network was constructed using STRING and Cytoscape software to obtain ten key genes with high connectivity.The pathview software was used to further study the expression of key genes in the pathway and the way in which they function,Kaplan-Meier plotter was used to draw survival curves in relation with key genes.Results A total of 87 DEGs were obtained from the screening,mainly involving pathways of immune response and inflammation.Ten key genes with high connectivity were obtained from PPI network and Cytoscape software including ICAM1,TLR2,CXCL8,GAPDH,CXCL10,IL-18,CXCL1,CXCL2,CXCL12,PTGS2.Pathview study found that key genes were mainly expressed and functioned in phagosome,Toll-like receptor signaling pathway,antigen processing and presentation pathways.Survival analysis showed that the high expression of TLR2,CXCL10,CXCL12,and IL-18 and low expression of CXCL8,GAPDH,and CXCL1 were significantly related to the disease-free survival and poor overall survival of patients with endometrioid ovarian cancer.Conclusion The differentially expressed immune-related genes in endometrioid ovarian cancer may regulate inflammation and immune response to form a suitable tumor microenvironment for immunity escape,resulting in the occurrence and development of endometrioid ovarian cancer.
作者
陈聪
倪乐宜
陈育梅
CHEN Cong;NI Leyi;CHEN Yumei(Department of Gynecology,Wenzhou People's Hospital,Wenzhou 325000,China)
出处
《浙江医学》
CAS
2021年第14期1526-1530,I0002,I0003,共7页
Zhejiang Medical Journal
