Immune-Related Gene SERPINE1 Is a Novel Biomarker for Diffuse Lower-Grade Gliomas via Large-Scale Analysis.
Immune-Related Gene SERPINE1 Is a Novel Biomarker for Diffuse Lower-Grade Gliomas via Large-Scale Analysis.
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通过大规模分析发现免疫相关基因 SERPINE1 是弥漫性低级别胶质瘤的新型生物标志物
DOI：
10.3389/fonc.2021.646060
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发表时间：
2021
影响因子：
4.7
通讯作者：
Xin T
中科院分区：
文献类型：
--
作者：
Huang X;Zhang F;He D;Ji X;Gao J;Liu W;Wang Y;Liu Q;Xin T
背景胶质瘤是中枢神经系统高度致命性的原发肿瘤之一。免疫细胞作为肿瘤微环境(TME)的重要组成部分，在弥漫性低级别胶质瘤(LGGs)的进展和预后中起着至关重要的作用。本研究旨在通过对TCGA数据库的研究，筛选出LGGS的关键免疫相关因子。方法在TCGA数据库中下载508例LGG患者的RNA测序数据。采用ESTIMATE算法计算基质评分、免疫评分和评分，在此基础上利用LIMMA软件对差异表达基因(DEG)进行分析。COX回归分析和Cytoscape软件的cell Hubba插件筛选生存相关基因和HUB基因，这些基因的交集导致在LGG中发挥关键作用的SERPINE1的鉴定。通过对TCGA数据库的数据挖掘，进一步分析SERPINE1在LGGs中的表达模式、临床特征和调控机制。此外，上述对SERPINE1的分析在CGGA数据库中的LGG队列中得到了进一步的验证。结果间质和免疫细胞的浸润与LGGs的预后和恶性程度密切相关。共筛选出54个生存相关基因和46个HUB基因，其中SERPINE1在LGG组织中的表达显著高于正常组织。此外，SERPINE1在WHO分级为III级的胶质瘤和IDH野生型中的表达更为明显，其表达与LGG患者的预后不良有关。COX回归分析也证实了SERPINE1在LGG患者中的独立预后价值。从SERPINE1的功能来看，富集分析结果表明，SERPINE1主要在免疫相关的生物学过程和信号通路中富含。此外，它还与免疫细胞在免疫球蛋白微环境中的渗透密切相关，并与PD1、PD-L1、PD-L2协同作用。结论SERPINE1可作为判断LGGs预后的生物标志物和潜在的免疫治疗靶点。
Background Glioma is one of the highly fatal primary tumors in the central nervous system. As a major component of tumor microenvironment (TME), immune cell has been proved to play a critical role in the progression and prognosis of the diffuse lower-grade gliomas (LGGs). This study aims to screen the key immune-related factors of LGGs by investigating the TCGA database. Methods The RNA-sequencing data of 508 LGG patients were downloaded in the TCGA database. ESTIMATE algorithm was utilized to calculate the stromal, immune, and ESTIMATE scores, based on which, the differentially expressed genes (DEGs) were analyzed by using “limma” package. Cox regression analysis and the cytoHubba plugin of Cytoscape software were subsequently applied to screen the survival-related genes and hub genes, the intersection of which led to the identification of SERPINE1 that played key roles in the LGGs. The expression patterns, clinical features, and regulatory mechanisms of SERPINE1 in the LGGs were further analyzed by data mining of the TCGA database. What’s more, the above analyses of SERPINE1 were further validated in the LGG cohort from the CGGA database. Result We found that stromal and immune cell infiltrations were strongly related to the prognosis and malignancy of the LGGs. A total of 54 survival-related genes and 46 hub genes were screened out in the DEGs, within which SERPINE1 was identified to be significantly overexpressed in the LGG samples compared with the normal tissues. Moreover, the upregulation of SERPINE1 was more pronounced in the gliomas of WHO grade III and IDH wild type, and its expression was correlated with poor prognosis in the LGG patients. The independent prognostic value of SERPINE1 in the LGG patients was also confirmed by Cox regression analysis. In terms of the functions of SERPINE1, the results of enrichment analysis indicated that SERPINE1 was mainly enriched in the immune‐related biological processes and signaling pathways. Furthermore, it was closely associated with infiltrations of immune cells in the LGG microenvironment and acted synergistically with PD1, PD-L1, PD-L2. Conclusion These findings proved that SERPINE1 could serve as a prognostic biomarker and potential immunotherapy target of LGGs.
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DOI：
10.1016/j.nicl.2018.10.014
发表时间：
2018
期刊：
NeuroImage. Clinical
影响因子：
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作者：
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DOI：
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发表时间：
2018-04-16
期刊：
Aging
影响因子：
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影响因子：
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DOI：
10.1056/nejmoa1402121
发表时间：
2015-06-25
期刊：
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影响因子：
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Zhang J
影响因子：
7.5
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Li, Sijing;Wei, Xiaohui;Sun, Li
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