PLAT基因在胶质瘤中的作用:联合转录组、单细胞转录组和空间转录组的研究  

Role of PLAT genes inglioma:combined transcriptome,single-cell transcriptome,and spatial transcriptome studies

作　　者：哈丽比热·艾尼瓦尔 范海 玉素甫·司马义 高代熹 孜拉来·艾尔肯 李汶洳 朱国华[1] Ainiwaer Halibire;Hai Fan;Simayi Yusufu;Daixi Gao;Aierken Zilalai;Wenru Li;Guohua Zhu(Department of Neurosurgery,The First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China)

机构地区：[1]新疆医科大学第一附属医院神经外科,乌鲁木齐830054

出　　处：《中华脑科疾病与康复杂志(电子版)》2024年第6期325-333,共9页Chinese Journal of Brain Diseases and Rehabilitation(Electronic Edition)

基　　金：新疆医科大学第一附属医院青年科研启航专项基金(2022YFY-QKQN-62)

摘　　要：目的通过癌症基因组图谱(TCGA)和基因表达量关联数据库(GTEx)探究组织型纤溶酶原激活物(PLAT)基因在胶质瘤中的表达及预后,为胶质瘤诊断及治疗提供靶点。方法利用TCGA和GTEx数据库分析PLAT在胶质瘤组织和正常组织间的表达差异,以及PLAT表达水平与临床病理参数[如性别、年龄、异柠檬酸脱氢酶(IDH)启动子突变状态和1p/19q是否共缺失等]之间的关系。采用Kaplan-Meier生存分析评估PLAT对胶质瘤患者预后的影响,采用基因本体及京都基因和基因组百科全书数据库富集分析筛选分子功能和信号通路,使用CIBERSORT算法分析免疫浸润水平与胶质瘤中PLAT表达水平的相关性,进行单细胞转录组测序和空间转录组测序。结果PLAT在胶质瘤中高表达(P=0.002,95%CI:0.06~0.30),并且在年龄>60岁(P<0.05,95%CI:1.26~1.88)、IDH野生型(P<0.05,95%CI:-2.79~-2.46)和1p/19q未共缺失型(P<0.05,95%CI:-1.41~-0.87)患者中也表现出高表达。PLAT上调与胶质瘤患者更差的总生存期(OS)相关(HR=6.48,95%CI:4.81~8.74,P<0.001),并具有较高的诊断价值[曲线下面积(AUC)=0.931],基于PLAT表达水平预测的胶质瘤患者1、3和5年生存率AUC值均高于0.7。信号通路分析显示,PLAT显著相关的通路有神经活性配体-受体相互作用、细胞因子-细胞因子受体相互作用、IL-17信号通路。PLAT的表达与肿瘤免疫微环境中巨噬细胞M0、滤泡辅助性T细胞的浸润水平呈正相关,与单核细胞的浸润水平呈负相关。单细胞转录组分析显示,PLAT在间充质样细胞和少突胶质细胞祖细胞中显著表达。空间转录组分析显示,PLAT主要分布在靠近肿瘤细胞的位置,与前述定位结果高度一致,且PLAT表达量与肿瘤细胞含量呈正相关。结论PLAT的表达水平在胶质瘤中显著升高,并与更差的生存率相关,是诊断、治疗及预后的潜在肿瘤标志物。Objective To investigate the expression and prognosis of plasminogen activator(PLAT)gene in glioma through The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx),and to provide a target for the diagnosis and treatment ofglioma.Methods The TCGA and GTEx databases were used to analyze the expression difference of PLAT between gliomatissues and normal tissues.The relationship between PLAT expression level and clinicopathological parameters such as gender,age,isocitrate dehydrogenase(IDH)promoter mutation status and 1p/19q co-deletion;Kaplan-Meier survival analysis of the prognostic value of PLAT in glioma;Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were used to screen molecular functions and signaling pathways.CIBERSORT algorithm was used to analyze the correlation between immune infiltration level and PLAT expression level in glioma.Single-cell transcriptome sequencing and spatial transcriptome sequencing were performed.Results PLAT was highly expressed in glioma(P=0.002,95%CI:0.06-0.30),and was also expressed in 1p/19q non-codeletion[P<0.05,95%CI:-2.79-(2.46)],IDH wild-type[P<0.05,95%CI:-2.79-(2.46)],patients aged>60 years(P<0.05,95%CI:1.26-1.88),yet was no statistically significant difference in expression between males and females(P>0.05).Upregulation of PLAT gene was associated with worse overall survival(OS)in glioma patients(HR=6.48,95%CI:4.81-8.74,P<0.001)and had a high diagnostic value[area under the curve(AUC)=0.931].The AUC values for predicting of the 1-,3-,and 5-year survival rates of glioma patients based on PLAT expression levels were higher than 0.7.Signal pathway analysis showed that PLAT gene included neuroactive ligand-receptor interaction,cytokine-cytokine receptor interaction and IL-17 signaling pathway.In addition,PLAT expression was positively correlated with the infiltration level of macrophage M0 and follicular helper T cells in the tumor immune microenvironment,but negatively correlated with the infiltration level of monocytes.Single-cell transcr

关 键 词：组织型纤溶酶原激活物基因 胶质瘤 表达差异 预后 多组学 

分 类 号：R739.41[医药卫生—肿瘤]