Prognosis and immune features of pyroptosis-related RNA patterns in low-grade glioma.
Prognosis and immune features of pyroptosis-related RNA patterns in low-grade glioma.
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DOI：
10.3389/fonc.2022.1015850
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发表时间：
2022
影响因子：
4.7
通讯作者：
Tao, Tao
中科院分区：
文献类型：
--
作者：
Liu, Hanzhang;Tao, Tao
低级别胶质瘤（LGG）是恶性原发性脑肿瘤，在年轻人中更常见。细胞凋亡是一种程序性细胞死亡的炎症形式，近年来已被证明与肿瘤生长和肿瘤微环境（TME）直接相关。然而，LGG和焦亡之间的相关性仍有待探讨。在这项研究中，我们探讨了热解相关基因的表达模式及其预后意义的基础上，转录组和临床数据在LGG。我们确定了31个pyropetosis-related基因的差异表达在mRNA水平之间的数据LGG患者从TCGA和数据的正常脑组织从GTEx。单因素考克斯回归分析筛选出16个与生存期相关的差异表达基因。接下来，使用LASSO考克斯回归建立预后模型，该模型将LGG患者分为高风险和低风险亚组，并显示CGGA测试队列中总生存期（OS）与临床因素组合的独立预后值。通过CIBERSORT R软件包和TIMER数据库将Pyroptosis和免疫细胞相关联。通过对523例LGG和1152例正常组织的分析，筛选出9个差异显著的基因。当结合风险评分和临床因素时，AUC保持在约0.74。富集分析显示，DEG主要富集在嘌呤-细胞因子受体相互作用、免疫应答和趋化因子信号通路中。免疫细胞富集分析显示，大多数免疫细胞类型的得分在高风险组和低风险组之间存在显著差异，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。热解相关基因在LGG中起着关键作用，并与肿瘤免疫相关，这可能有利于LGG的预后和免疫治疗。
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. 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. 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. 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.
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