■胶质瘤是中枢神经系统最常见的原发性肿瘤之一。先前的研究发现巨噬细胞积极参与肿瘤的生长。
■使用加权基因共表达网络分析来鉴定用于聚类的有意义的巨噬细胞相关基因基因。Pamr,SVM,和神经网络用于验证聚类结果。体细胞突变和甲基化用于定义鉴定的簇的特征。进行弹性回归和主成分分析后,分层组之间的差异表达基因(DEGs)用于构建MScore。基于单细胞测序分析在肿瘤微环境中评估巨噬细胞特异性基因的表达。来自15个神经胶质瘤数据集的总共2365个样品和5842个泛癌症样品用于MScore的外部验证。
■巨噬细胞与神经胶质瘤患者的生存率呈负相关。通过弹性回归和PCA获得的26个巨噬细胞特异性DEGs在巨噬细胞中在单细胞水平上高表达。通过浸润微环境的活跃促炎和代谢谱以及对具有该特征的样品的免疫疗法的反应,验证了MScore在神经胶质瘤中的预后价值。MScore设法在15个外部神经胶质瘤数据集和泛癌症数据集中对患者生存概率进行分层,这预测了更糟糕的生存结果。湘雅胶质瘤队列的测序数据和免疫组织化学证实了MScore的预后价值。基于MScore的预后模型显示出较高的准确率。
■我们的发现强烈支持巨噬细胞的调节作用,特别是M2巨噬细胞在神经胶质瘤的进展和值得进一步的实验研究。
UNASSIGNED: Gliomas are one of the most common types of primary tumors in central nervous system. Previous studies have found that macrophages actively participate in tumor growth.
UNASSIGNED: Weighted gene co-expression network analysis was used to identify meaningful macrophage-related gene genes for clustering. Pamr, SVM, and neural network were applied for validating clustering results. Somatic mutation and methylation were used for defining the features of identified clusters. Differentially expressed genes (DEGs) between the stratified groups after performing elastic regression and principal component analyses were used for the construction of MScores. The expression of macrophage-specific genes were evaluated in tumor microenvironment based on single cell sequencing analysis. A total of 2365 samples from 15 glioma datasets and 5842 pan-cancer samples were used for external validation of MScore.
UNASSIGNED: Macrophages were identified to be negatively associated with the survival of glioma patients. Twenty-six macrophage-specific DEGs obtained by elastic regression and PCA were highly expressed in macrophages at single-cell level. The prognostic value of MScores in glioma was validated by the active proinflammatory and metabolic profile of infiltrating microenvironment and response to immunotherapies of samples with this signature. MScores managed to stratify patient survival probabilities in 15 external glioma datasets and pan-cancer datasets, which predicted worse survival outcome. Sequencing data and immunohistochemistry of Xiangya glioma cohort confirmed the prognostic value of MScores. A prognostic model based on MScores demonstrated high accuracy rate.
UNASSIGNED: Our findings strongly support a modulatory role of macrophages, especially M2 macrophages in glioma progression and warrants further experimental studies.