滨州医学院学报2024,Vol.47Issue(3) :206-216,222.DOI:10.19739/j.cnki.issn1001-9510.2024.03.009

构建低级别胶质瘤免疫浸润模式相关的ceRNA调控网络和预后模型

Construction of ceRNA regulatory network and prognostic model related to the immune infiltration pattern of low-grade glioma

刘静远 夏子怡 刘沅雨 卢云霞 董耀 许森 刘文英
滨州医学院学报2024,Vol.47Issue(3) :206-216,222.DOI:10.19739/j.cnki.issn1001-9510.2024.03.009

构建低级别胶质瘤免疫浸润模式相关的ceRNA调控网络和预后模型

Construction of ceRNA regulatory network and prognostic model related to the immune infiltration pattern of low-grade glioma

刘静远 1夏子怡 2刘沅雨 3卢云霞 3董耀 4许森 5刘文英3
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作者信息

  • 1. 滨州医学院第二临床医学院 山东 烟台 264003
  • 2. 滨州医学院中西医结合学院 山东 烟台 264003
  • 3. 滨州医学院药学院(葡萄酒学院) 山东 烟台 264003
  • 4. 滨州医学院口腔医学院 山东 烟台 264003
  • 5. 滨州医学院基础医学院生物化学与分子生物学教研室 山东 烟台 264003
  • 折叠

摘要

目的 构建新型免疫浸润模式相关ceRNA调控网络及低级别胶质瘤(LGG)预后模型.结合肿瘤微环境揭示ceRNA调控网络在LGG患者风险评估和预后评估中的作用.方法 从TCGA和CGGA数据库中获取具有完整生存信息的LGG患者数据,构建新的免疫浸润模式相关的ceRNA调控网络和预后模型,并通过外部数据库、RT-qPCR和West-ern blot进行验证.结果 在LGG中应用浸润评分作为分组依据,构建免疫相关的ceRNA网络和预后风险最优模型分析发现,高危组的肿瘤免疫和炎症相关信号通路的激活增强,免疫反应状态升高.免疫评分升高与预后不良显著相关,风险评分在临床特征变化后仍可作为独立的预后因素,提示局部免疫状态或在预后中具有更好的潜力.通过分析各种免疫细胞类型的浸润丰度,发现CD8+T细胞、M0型巨噬细胞在预后较差的高危组中浸润水平相对较高.探索了目前常用的47个免疫检查点,发现大多数经典检查点的表达水平在高风险组显著高于低风险组.通过qRT-PCR和Western blot对预后评估模型的建模基因进行评估,揭示了ST8SIA2和SLC10A4在胶质瘤表达升高,具有潜在的免疫治疗和预后预测的价值.结论 风险评分模型和预后模型可用于LGG患者的风险评价和预后评估.

Abstract

Objective To construct a novel ceRNA regulatory network related to immune infiltration pattern and a low-grade gliomas (LGG)prognosis model,and to reveal the role of ceRNA regulatory network in risk assessment and prognosis evaluation of LGG patients in combination with tumor microenvironment.Methods The data of LGG patients with complete survival infor-mation were obtained from the TCGA and CGGA databases,and a new ceRNA regulatory network and a prognostic model related to immune infiltration patterns were constructed and verified by external databases,RT-qPCR and Western blot.Results Using the infiltration score in LGG as the basis for grouping,after the construction of immune-related CeRNA network and the analysis of optimal prognostic risk model,we found that the activation of tumor immune and inflammation-related signaling pathways was enhanced in the high-risk group,and the state of immune response was elevated. The increase of the immune score was signifi cantly associated with poor prognosis,and the risk score could be used as an independent prognostic factor after changes in clini-cal features,suggesting that the local immune status might have a better prognosis. By analyzing the abundance of various im-mune cell types,we found that the infiltration level of CD8+T cells and M0 type macrophages was relatively high in the high risk group with poor prognosis. We explored 47 common immune checkpoints and found that the expression levels of most of the clas-sical checkpoints were significantly higher in the high-risk group than those in the low-risk group. QRT-PCR and Western blot were used to evaluate the model genes of the prognostic evaluation model,which revealed that the expression of ST8SIA2 and SLC10A4 was elevated in glioma,which had potential value for immunotherapy and prognosis prediction.Conclusion The risk scoring model and the prognostic model can be used for risk assessment and prognostic evaluation of LGG patients.

关键词

低级别胶质瘤/免疫浸润/ceRNA网络/预后模型/生存预测

Key words

low-grade glioma/immune infiltration/ceRNA network/prognostic model/survival prediction

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基金项目

山东省医药卫生科技发展计划(2016WS0007)

出版年

2024
滨州医学院学报
滨州医学院

滨州医学院学报

影响因子:0.548
ISSN:1001-9510
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