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胶质母细胞瘤血管生成相关基因特征衍生的风险评分:预测胶质母细胞瘤预后和免疫异质性的前景

Angiogenesis-Related Gene Signature-Derived Risk Score for Glioblastoma: Prospects for Predicting Prognosis and Immune Heterogeneity in Glioblastoma.

作者信息

Wang Gang, Hu Jin-Qu, Liu Ji-Yuan, Zhang Xiao-Mei

机构信息

Department of Neurosurgery, The First Affiliated Hospital of China Medical University, Shenyang, China.

Department of Rheumatology and Immunology, ShengJing Hospital of China Medical University, Shenyang, China.

出版信息

Front Cell Dev Biol. 2022 Mar 18;10:778286. doi: 10.3389/fcell.2022.778286. eCollection 2022.

Abstract

Glioblastoma multiforme (GBM) is the most common malignant tumor in the central nervous system with poor prognosis and unsatisfactory therapeutic efficacy. Considering the high correlation between tumors and angiogenesis, we attempted to construct a more effective model with angiogenesis-related genes (ARGs) to better predict therapeutic response and prognosis. The ARG datasets were downloaded from the NCBI-Gene and Molecular Signatures Database. The gene expression data and clinical information were obtained from TCGA and CGGA databases. The differentially expressed angiogenesis-related genes (DE-ARGs) were screened with the R package "DESeq2". Univariate Cox proportional hazards regression analysis was used to screen for ARGs related to overall survival. The redundant ARGs were removed by least absolute shrinkage and selection operator (LASSO) regression analysis. Based on the gene signature of DE-ARGs, a risk score model was established, and its effectiveness was estimated through Kaplan-Meier analysis, ROC analysis, etc. A total of 626 DE-ARGs were explored between GBM and normal samples; 31 genes were identified as key DE-ARGs. Then, the risk score of ARG signature was established. Patients with high-risk score had poor survival outcomes. It was proved that the risk score could predict some medical treatments' response, such as temozolomide chemotherapy, radiotherapy, and immunotherapy. Besides, the risk score could serve as a promising prognostic predictor. Three key prognostic genes (PLAUR, ITGA5, and FMOD) were selected and further discussed. The angiogenesis-related gene signature-derived risk score is a promising predictor of prognosis and treatment response in GBM and will help in making appropriate therapeutic strategies.

摘要

多形性胶质母细胞瘤(GBM)是中枢神经系统中最常见的恶性肿瘤,预后较差,治疗效果不尽人意。考虑到肿瘤与血管生成之间的高度相关性,我们试图构建一个更有效的血管生成相关基因(ARG)模型,以更好地预测治疗反应和预后。从NCBI基因和分子特征数据库下载ARG数据集。基因表达数据和临床信息分别从TCGA和CGGA数据库获取。使用R包“DESeq2”筛选差异表达的血管生成相关基因(DE-ARG)。采用单因素Cox比例风险回归分析筛选与总生存相关的ARG。通过最小绝对收缩和选择算子(LASSO)回归分析去除冗余的ARG。基于DE-ARG的基因特征建立风险评分模型,并通过Kaplan-Meier分析、ROC分析等评估其有效性。共探索了GBM与正常样本之间的626个DE-ARG;31个基因被确定为关键DE-ARG。然后,建立了ARG特征的风险评分。高风险评分的患者生存结果较差。结果证明,该风险评分可以预测一些医学治疗的反应,如替莫唑胺化疗、放疗和免疫治疗。此外,该风险评分可作为一个有前景的预后预测指标。选择了三个关键预后基因(PLAUR、ITGA5和FMOD)并进行了进一步讨论。血管生成相关基因特征衍生的风险评分是GBM预后和治疗反应的一个有前景的预测指标,将有助于制定合适的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bac0/8971933/0665cb225a5d/fcell-10-778286-g001.jpg

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