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一种用于胶质瘤的替代性多聚腺苷酸化相关长链非编码RNA预后特征的鉴定与验证

Identification and Verification of an Alternative Polyadenylation-Related lncRNA Prognostic Signature for Glioma.

作者信息

Wang Hui, Jiang ZhiJun

机构信息

Department of Pathology, The First People's Hospital of Fuyang, Hangzhou City, Zhejiang Province 31400, China.

出版信息

Comput Math Methods Med. 2022 Sep 7;2022:2164229. doi: 10.1155/2022/2164229. eCollection 2022.

Abstract

Due to the high mortality and modality of glioma, it was urgently needed to develop a glioma prognostic assessment system. Previous studies demonstrated that alternative polyadenylation- (APA-) related genes are important in immune response and oncogenesis. mRNA and lncRNA expression information of glioma samples were acquired from CGGA and TCGA databases, and lncRNAs associated with APA were selected through correlation analysis. The prognosis model of APA-related lncRNAs was built by the univariate Cox, random forest, and univariate Cox regression analyses. Glioma samples were assigned into high- and low-risk groups. Independence and effectiveness of the prognostic model were evaluated by Kaplan-Meier analysis, ROC curve, and Cox regression analyses. GO, KEGG enrichment, and GSEA analyses showed that the mainly involved signaling pathways were enriched in cellular immunity and immune signal transduction. We further analyzed expression differences of negative immune regulatory genes and immune cell infiltration degree between two groups. Immune checkpoints CTLA4 and LAG3 and immune suppressors TGFB, IL10, NOS3, and IDO1 and immune cell infiltration were notably upregulated in the high-risk group. The PD1/PDL1 expression was significantly correlated with risk score, showing that the prognostic model of APA-related lncRNA could effectively assess the tumor immune suppression. In conclusion, we established a risk assessment model of APA-related lncRNA in glioma, which could effectively evaluate prognosis of patients with glioma and tumor immune suppression and could provide guidance for clinical treatment.

摘要

由于胶质瘤的高死亡率和高侵袭性,迫切需要开发一种胶质瘤预后评估系统。先前的研究表明,可变聚腺苷酸化(APA)相关基因在免疫反应和肿瘤发生中很重要。从CGGA和TCGA数据库获取胶质瘤样本的mRNA和lncRNA表达信息,并通过相关性分析选择与APA相关的lncRNAs。通过单变量Cox、随机森林和单变量Cox回归分析建立APA相关lncRNAs的预后模型。将胶质瘤样本分为高风险组和低风险组。通过Kaplan-Meier分析、ROC曲线和Cox回归分析评估预后模型的独立性和有效性。GO、KEGG富集和GSEA分析表明,主要涉及的信号通路在细胞免疫和免疫信号转导中富集。我们进一步分析了两组之间负性免疫调节基因的表达差异和免疫细胞浸润程度。免疫检查点CTLA4和LAG3以及免疫抑制因子TGFB、IL10、NOS3和IDO1以及免疫细胞浸润在高风险组中显著上调。PD1/PDL1表达与风险评分显著相关,表明APA相关lncRNA的预后模型可以有效评估肿瘤免疫抑制。总之,我们建立了胶质瘤中APA相关lncRNA的风险评估模型,该模型可以有效评估胶质瘤患者的预后和肿瘤免疫抑制情况,并可为临床治疗提供指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23a7/11401696/834e2b33bc3c/CMMM2022-2164229.001.jpg

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