基于单细胞测序数据分析微环境中配体-受体对对IDH突变型脑胶质瘤预后的预测价值  

Prognostic value of ligand-receptor pairs in microenvironment based on single-cell sequencing data for IDH mutation gliomas

作　　者：张莹[1] 孙志延 陈乔冬 曾凡 王志亮 Zhang Ying;Sun Zhiyan;Chen Qiaodong;Zeng Fan;Wang Zhiliang(Molecular Neuropathology Unit,Beijing Neurosurgical Institute,Beijing Tiantan Hospital,Capital Medical University,Beijing 100070,China;Department of Neurosurgery,Beijing Tiantan Hospital,Capital Medical University,Beijing 100070,China)

机构地区：[1]北京市神经外科研究所分子神经病理室,首都医科大学附属北京天坛医院,100070 [2]首都医科大学附属北京天坛医院神经外科,100070

出　　处：《神经疾病与精神卫生》2025年第1期26-35,共10页Journal of Neuroscience and Mental Health

基　　金：国家自然科学基金(82102764,82272870);国家资助博士后研究人员计划(GZC20231749)。

摘　　要：目的分析异柠檬酸脱氢酶(IDH)突变型脑胶质瘤微环境中细胞通讯的特征及意义。方法利用Seurat和clusterProfiler分析IDH突变型脑胶质瘤组织中细胞类型、占比及功能,采用CellphoneDB分析细胞-细胞通讯特征并筛选有显著差异的配体-受体(LR)对,采用单因素Cox回归分析判断LR对表达与IDH突变型脑胶质瘤患者总体生存期的关系。基于LR对的表达与预后信息采用一致性聚类将患者分为不同亚型。采用Log-rank、基因集富集分析(GSEA)、ESTIMATE和CIBERSORT分别比较不同亚型患者的生存差异、功能差异以及免疫特征,根据LR对的表达相关性和最小绝对收缩和选择算子(LASSO)分析构建风险预测模型,分析风险评分与患者亚型、病理指标的关系。采用Kaplan-Meier生存曲线、Log-rank检验和Cox回归模型评价风险评分与IDH突变型脑胶质瘤患者生存期的关系。结果共获取了27154个细胞,注释后分为6个细胞类型。在CGGA693和CGGA325数据集的IDH突变患者中,分别有140个和131个LR对与患者预后有关(P<0.05),可将患者分为预后有显著差异的2个分子亚型(P<0.05)。与预后较好的亚型1相比,亚型2中Ⅳ级和1p/19q共缺失的脑胶质瘤患者占比更多(P<0.05)。Hallmark富集分析显示,亚型2与MYC靶基因、DNA修复、氧化磷酸化有关。KEGG通路富集分析显示,亚型2主要与核糖体、氧化磷酸化、帕金森病、亨廷顿病、阿尔茨海默病有关。与亚型1相比,亚型2的肿瘤纯度更低,免疫浸润程度更高。配体和受体的表达相关系数>0.5的LR对有14个,利用LASSO回归分析构建了由DLL4-NOTCH3、CXCL12-CXCR4、COPA-SORT1、PLAU-PLAUR和EPHB2-EFNB1组成的风险评分模型。LR对风险评分在亚型2中更高(P<0.05),其随病理级别的上升而增加(P<0.05);LR对风险评分在1p/19q共缺失组中更高(P<0.05);在IDH突变型、IDH突变及1p/19q非共缺失脑胶质瘤患者中,高风险组患者较低风险组生存期短(P<0.Objective To analyze the characteristics and significance of cell communication in the microenvironment of isocitrate dehydrogenase(IDH)mutation gliomas.Methods Seurat and clusterProfiler were used to analyze cell types,proportions,and functions in IDH mutation glioma tissues.CellphoneDB was used to analyze cell-cell communication characteristics and screen ligand-receptor(LR)pairs with significant differences.Univariate Cox regression was used to analyze the association between LR pairs expression and overall survival in IDH mutation glioma patients.Patients were classified into different subtypes using consistent clustering based on LR pairs expression and prognostic information.Log-rank,Gene Set Enrichment Analysis(GSEA),ESTIMATE,and CIBERSORT were used to compare the survival differences,functional differences,and immune characteristics of patients with different subtypes.Based on the correlation of LR pairs expression and least absolute shrinkage and selection operator(LASSO)analysis,a risk prediction model was constructed to analyze the association between risk scores,patient subtypes and pathological indicators.Kaplan-Meier survival curve,Log-rank test and Cox regression model were used to evaluate the relationship between risk score and survival of IDH mutation glioma patients.Results A total of 27154 cells were obtained,annotated and divided into six cell types.In the IDH mutation patients of CGGA693 and CGGA325 datasets,there were 140 and 131 LR pairs,respectively,that were associated with patient prognosis(P<0.05),and patients were divided into two molecular subtypes with significant differences in prognosis(P<0.05),and the differences were statistically significant.Compared with subtype 1 with good prognosis,subtype 2 had a higher proportion of glioma patients with gradeⅣand 1p/19q co deletion(P<0.05).Hallmark enrichment analysis showed that subtype 2 was associated with MYC target genes,DNA repair,and oxidative phosphorylation.KEGG pathway enrichment analysis showed that subtype 2 was mainly associ

关 键 词：神经胶质瘤 异柠檬酸脱氢酶突变 细胞通讯 配体-受体对 预后 肿瘤微环境 

分 类 号：R73[医药卫生—肿瘤]