细胞间粘附分子1在胶质母细胞瘤中的表达和生物学作用
Expression and biological role of intercellular adhesion molecule-1 in glioblastoma
丁辉 1陈申波 1羊良旺 1吴然 1叶富跃 1杨堃1
作者信息
- 1. 海南医科大学第一附属医院神经外科,海南 海口 570102
- 折叠
摘要
目的 探讨细胞间粘附分子1(intercellular adhesion molecule-1,ICAM1)对胶质母细胞瘤(glioblastoma,GBM)中的预后预测价值及其与免疫抑制的关系.方法 使用来自TCGA-GBM的表达和临床数据评估ICAMs mRNA的表达及临床预后价值.使用人类蛋白质图谱数据库评估ICAM1在胶质母细胞瘤组织、细胞中的表达.基于cBioPortal数据库分析GBM中ICAM1与其他mRNAs的相关性,选择与ICAM1最显著正相关的前100个基因通过DAVID数据库进行GO和通路分析.通过JASPAR数据库确认可能调控ICAM1表达的转录因子,并利用GEO数据库GSE65363数据集进行验证.利用CAMOIP数据库探讨ICAM1表达与免疫细胞浸润的关系.结果 ICAM1在GBM中高表达并与预后相关.ICAM1与间质型标记基因的表达呈正相关,而与前神经元型标记基因的表达呈负相关.NF-κB能够与ICAM1启动子结合并调控ICAM1的表达.此外,ICAM1参与免疫反应,ICAM1的高表达促进了巨噬细胞的极化;同时,ICAM1与免疫抑制基因呈高度正相关.结论 ICAM1是 GBM发生前神经元型向间质型转变的始动因素之一,并在GBM免疫抑制中发挥重要作用,可作为预测GBM患者预后的潜在生物标志物.
Abstract
Objective To investigate the prognostic value of intercellular adhesion molecule-1(ICAM1)in glioblastoma(GBM)and its relationship with immunosuppression.Methods Expression and clinical data from TCGA-GBM were used to evaluate ICAMs mRNA expression and its clinical prognostic value.The expression of ICAM1 in GBM tissues and cells was evaluated by using The Human Protein Atlas database.The correlation between ICAM1 and other mRNAs in GBM was analyzed based on the cBioPortal database,and the top 100 genes with the most significant positive correlation with ICAM1 were selected for GO and pathway analysis through the DAVID database.Transcription factors that may regulate ICAM1 expression were identified by using the JASPAR database and validated by using the GSE65363 dataset of the GEO database.The relationship between ICAM1 expression and immune cell infiltration was investigated by using the CAMOIP database.Results ICAM1 was highly expressed in GBM and was associated with prognosis.ICAM1 was positively correlated with the expression of Mesenchymal marker genes and negatively correlated with the expression of proneural marker genes.NF-κB,together with ICAM1,could initiate the promoter and regulate the expression of ICAM1.In addition,ICAM1 was involved in the immune response,and the high expression of ICAM1 promoted the polarization of macrophages.At the same time,ICAM1 was highly positively correlated with immunosuppressor genes.Conclusions ICAM1 is one of the initiating factors of PMT in GBM,and plays an important role in GBM immunosuppression,which can be used as a potential biomarker to predict the prognosis of GBM patients.
关键词
胶质母细胞瘤/细胞间粘附分子/前神经元型向间质型转变/免疫抑制/生物标志物Key words
Glioblastoma/Intercellular adhesion molecule/PN-MES transition/Immunosuppression/Biomarker引用本文复制引用
基金项目
国家自然科学基金资助项目(82060456)
海南省重点研发计划项目基金资助项目(ZDYF2022SHFZ088)
出版年
2024
NETL
NSTL
万方数据