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低级别胶质瘤中焦亡相关RNA模式的预后及免疫特征

Prognosis and immune features of pyroptosis-related RNA patterns in low-grade glioma.

作者信息

Liu Hanzhang, Tao Tao

机构信息

Morphology Laboratory, Medical College of Nantong University, Nantong, Jiangsu, China.

Department of Clinical Medicine, Ningbo College of Health Science, Ningbo, Zhejiang, China.

出版信息

Front Oncol. 2022 Dec 20;12:1015850. doi: 10.3389/fonc.2022.1015850. eCollection 2022.

Abstract

PURPOSE

Low-grade gliomas (LGG), which are malignant primary brain tumors, are more prevalent in young adults. Pyroptosis, an inflammatory form of programmed cell death, has been shown in recent years to be directly associated with tumor growth and tumor microenvironment (TME). However, the correlation between LGG and pyroptosis remained to be explored. In this research, we explored pyroptosis-related gene expression patterns and their prognostic significance based on transcriptome profiles and clinical data in LGG.

METHODS

We identified 31 pyroptosis-related genes differentially expressed at the mRNA level between the data of LGG patients from TCGA and the data of normal brain tissues from GTEx. Univariate Cox regression analysis was used to screen 16 differentially expressed genes (DEGs) based on survival data. Next, the prognostic model was established using LASSO Cox regression, which divided LGG patients into high- and low- risk subgroups and showed an independent prognostic value for overall survival (OS) combined with clinical factors in the CGGA test cohort. Pyroptosis and immune cells were correlated through the CIBERSORT R package and the TIMER database.

RESULTS

Based on the analyses of 523 LGG and 1152 normal tissues, nine significant differential genes were identified. The AUC remained at about 0.74 when combined with the risk score and clinical factors. Enrichment analyses revealed that DEGs were mainly enriched in cytokine-cytokine receptor interactions, immune response and chemokine signaling pathways. Immune cell enrichment analysis demonstrated that scores for most immune cell types differed significantly between the high-and low-risk groups, and further infiltrating analysis showed obvious differences between these two risk subgroups.

CONCLUSION

Pyroptosis-related genes play a pivotal role in LGG and are associated with tumor immunity, which may be beneficial to the prognosis and immunotherapy of LGG.

摘要

目的

低级别胶质瘤(LGG)是恶性原发性脑肿瘤,在年轻成年人中更为常见。近年来,细胞焦亡作为程序性细胞死亡的一种炎症形式,已被证明与肿瘤生长和肿瘤微环境(TME)直接相关。然而,LGG与细胞焦亡之间的相关性仍有待探索。在本研究中,我们基于LGG的转录组谱和临床数据,探索了细胞焦亡相关基因的表达模式及其预后意义。

方法

我们在来自TCGA的LGG患者数据和来自GTEx的正常脑组织数据之间,鉴定出31个在mRNA水平上差异表达的细胞焦亡相关基因。使用单变量Cox回归分析基于生存数据筛选出16个差异表达基因(DEG)。接下来,使用LASSO Cox回归建立预后模型,该模型将LGG患者分为高风险和低风险亚组,并在CGGA测试队列中结合临床因素显示出对总生存期(OS)的独立预后价值。通过CIBERSORT R包和TIMER数据库将细胞焦亡与免疫细胞相关联。

结果

基于对523个LGG组织和1152个正常组织的分析,鉴定出9个显著差异基因。与风险评分和临床因素相结合时,AUC保持在约0.74。富集分析表明,DEG主要富集在细胞因子-细胞因子受体相互作用、免疫反应和趋化因子信号通路中。免疫细胞富集分析表明,高风险组和低风险组之间大多数免疫细胞类型的评分存在显著差异,进一步的浸润分析显示这两个风险亚组之间存在明显差异。

结论

细胞焦亡相关基因在LGG中起关键作用,并与肿瘤免疫相关,这可能对LGG的预后和免疫治疗有益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfd9/9808047/aa32521f5cf9/fonc-12-1015850-g001.jpg

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