摘要
目的基于生物信息学分析HMGA2基因在脑胶质瘤中的表达和预后意义,并推断HMGA2对脑胶质瘤发生、发展的生物学功能。方法从中国脑胶质瘤基因组图谱数据库(Chinese Glioma Genome Atlas,CGGA)和癌症基因组图谱(the Cancer Genome Atlas,TCGA)中各自获取693例和697例脑胶质瘤的基因表达数据集以及临床信息数据集,对HMGA2的不同表达状态进行研究。采用Kaplan-Meier生存曲线法和Cox分析法分析HMGA2对脑胶质瘤预后的预测价值。通过基因本体论(gene ontology,GO)分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析预测HMGA2可能富集的通路。将HMGA2与血管生成相关基因集进行基因集变异分析(gene set variation analysis,GSVA)。结果HMGA2在胶质瘤高级别、异柠檬酸脱氢酶(isocitrate dehydrogenase,IDH)野生型、无1p/19q共缺失的组别中高表达。生存分析显示,HMGA2较高表达脑胶质瘤患者的总生存期(overall survival,OS)显著低于HMGA2较低表达的OS(P<0.0001)。在Cox回归分析中,HMGA2表达水平是OS的独立预后因素。GO和KEGG分析显示,HMGA2富集在血管生成、内质网腔、细胞凋亡、肿瘤中的蛋白聚糖、蛋白结合、细胞外基质与受体的相互作用、焦点黏附、PI3KAKT信号通路等。GSVA结果显示HMGA2表达与血管生成呈正相关。结论HMGA2的表达与脑胶质瘤的病理级别和分子标志物密切相关,HMGA2高表达的脑胶质瘤患者预后较差,HMGA2能够影响胶质瘤的发生、发展,有望作为脑胶质瘤患者的预测标志物和治疗靶点。
OBJECTIVE To analyze the expression and prognostic significance of HMGA2 gene in brain glioma based on bioinformatics,and to infer the biological function of HMGA2 on the occurrence and development of brain glioma.METHODS The gene expression and clinical data sets of 693 and 697 glioma cases were obtained from the Chinese Glioma Genome Atlas(CGGA)and the Cancer Genome Atlas(TCGA),respectively,and the different expression states of HMGA2 were studied.Kaplan-Meier survival curve method and Cox analysis method were used to analyze the prognostic value of HMGA2 in brain glioma.Both gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were employed to predict the pathways potentially enriched by HMGA2.HMGA2 and angiogenesis related gene sets were analyzed for gene set variation(GSVA).RESULTS In the group with high-grade glioma,wild-type isocitrate dehydrogenase(IDH),and no 1p/19q codeletion,HMGA2 was highly expressed.Survival analysis showed that overall survival(OS)of patients with higher HMGA2 expression was significantly lower than that of patients with lower HMGA2 expression(P<0.0001).In Cox regression analysis,HMGA2 expression level was an independent prognostic factor for OS.GO and KEGG analysis showed that HMGA2 was enriched in angiogenesis,endoplasmic reticulum lumen,apoptosis,proteoglycans in cancer,protein binding,extracellular matrix and receptor interaction,focal adhesion signaling,PI3K-AKT pathway,etc.The results of GSVA showed that HMGA2 expression was positively correlated with angiogenesis.CONCLUSION The expression of HMGA2 is closely related to the pathological grade and molecular markers of brain glioma,and the prognosis of brain glioma patients with high expression of HMGA2 is poor.HMGA2 can affect the occurrence and development of glioma,and is expected to be used as a predictive marker and therapeutic target for brain glioma patients.
作者
冯佳宁
王倩
张志兰
宗丽霞
张志斐
杨兆勇
FENG Jianing;WANG Qian;ZHANG Zhilan;ZONG Lixia;ZHANG Zhifei;YANG Zhaoyong(North China University of Science and Technology,Tangshan 063000,China;Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China)
出处
《中国现代应用药学》
北大核心
2025年第14期2453-2460,共8页
Chinese Journal of Modern Applied Pharmacy
