胶质母细胞瘤早期复发和假性进展的癌症免疫差异表达基因分析及活性化合物预测  

Analysis of cancer-immune differentially expressed genes and prediction of active compounds in progression and pseudo-progression of glioblastoma

作　　者：孙瑞 赵梦洁 唐祥龙 李泰平[2] 肖红 SUN Rui;ZHAO Mengjie;TANG Xianglong;LI Taiping;XIAO Hong(College of Pharmacy,Nanjing Medical University,Nanjing 211166,China;不详)

机构地区：[1]南京医科大学药学院,南京211166 [2]南京医科大学附属脑科医院神经精神病学研究所 [3]芜湖市中医医院药剂科

出　　处：《临床神经外科杂志》2025年第1期39-46,共8页Journal of Clinical Neurosurgery

基　　金：国家自然科学基金资助项目(81902535)。

摘　　要：目的对早期复发和假性进展胶质母细胞瘤的癌症免疫差异基因进行研究分析并预测活性化合物。方法在高通量基因表达(GEO)数据库中选择GSE231994数据集作为主要分析对象,筛选二次手术后早期复发和假性进展病例样本之间的免疫相关差异基因,进行基因本体论(GO)生物过程(BP)和京都基因与基因组百科全书(KEGG)分析,构建蛋白质-蛋白质相互作用(PPI)网络,获得枢纽基因。应用TCMSP计算系统生物学实验室平台数据库预测可能有效的活性化合物,并在CB-Dock2服务器进行分子对接实验。结果GSE231994数据集筛选得到140差异表达基因,其中上调基因50个,下调基因90个,其中核心基因有IL1B、IL10、CXCL8、EGFR、TLR2、CD68、CXCR4、ITGB2、CD163和CSF1R,主要参与炎症反应、信号转导和免疫反应生物过程,以及富集于癌症途径、细胞因子-细胞因子受体相互作用和PI3K/Akt信号通路。根据度值选取前三个基因,通过TCMSP平台预测得到槲皮素可能为有效化合物。对接结果显示槲皮素与IL1B具有更好的结合能力。结论通过生物信息手段分析揭示免疫表达基因IL1B、IL10和CXCL8与胶质母细胞瘤早期复发和假性进展有着密切的关系,而槲皮素可作为干预的有效活性化合物。Objective To study and analyze cancer-immune differentially expressed genes in progression and pseudo-progression glioblastoma,and predict active compounds.Methods The GSE231994 dataset was selected as the main analysis dataset in the Gene Expression Omnibus(GEO)database,and immune related differentially expressed genes were screened between samples of progression and pseudo-progression cases after secondary surgery.Biological Process(BP)of Gene Ontology(GO),and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were performed to construct a protein-protein interaction(PPI)network and obtain hub genes.The TCMSP platform was applied to predict potentially active compounds,and molecular docking was accomplished on the CB Dock2 server.Results One hundred and forty differentially expressed genes were screened from the GSE231994 dataset,including 50 up-regulated genes and 90 down-regulated genes.The core genes included IL1B,IL10,CXCL8,EGFR,TLR,CD68,CXCR4,ITGB,CD16,and CSF1R,which mainly participated in inflammatory response,signal transduction,and immune response biological processes,as well as were enriched in the cancer pathway,cytokine-cytokine receptor interaction,and PI3K/Akt signaling pathways.The top three genes based on degree values were selected to predict,and quercetin may be an bio-active compound.The molecular docking results showed that quercetin had better binding ability with IL1B.Conclusions It is revealed that immune expression genes IL1B,IL10,and CXCL8 are closely related to progression and pseudo-progression of glioblastoma,and quercetin can serve as an effective active compound for intervention via bioinformatics analysis.

关 键 词：早期复发 假性进展 胶质母细胞瘤 生物信息学 差异基因 

分 类 号：R739.41[医药卫生—肿瘤]