鉴定神经坏死性相关长链非编码 RNA 与脑胶质瘤分子亚型的预后特征。

Identification of Prognostic Signature of Necroptosis-Related lncRNAs and Molecular Subtypes in Glioma.

机构信息

Neurovascular Center, Changhai Hospital, Naval Medical University, Shanghai 200003, China.

出版信息

Comput Math Methods Med. 2022 Sep 5;2022:3440586. doi: 10.1155/2022/3440586. eCollection 2022.

DOI:10.1155/2022/3440586

PMID:36110575

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9468935/

Abstract

BACKGROUND

In tumor progression and epigenetic regulation, long non-coding RNA (lncRNA) and necroptosis are crucial regulators. However, in glioma microenvironment, the role of necroptosis-related lncRNAs (NRLs) remains unknown.

METHOD

In this study, the RNA-seq and clinical annotation of glioma patients were analyzed using the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. To investigate prognosis and tumor microenvironment of NRLs in gliomas, we conducted a prediction model based on the training cohort. The accuracy of the model was verified in the verification cohort.

RESULTS

A signature composed of 13 NRLs was identified, and all glioma patients were divided into two groups. We found that each group has unique survival outcomes, biological behaviors, and immune infiltrating status. The necroptosis-related lncRNA signature (NRLS) model was found to be an independent risk factor in multivariate Cox analysis. Immunosuppressive microenvironment was positively correlated with the high-risk group. Due to significantly different IC50 between risk groups, NRLS could be used as a guide for chemotherapeutic treatment. Further, the entire cohort was divided into two clusters depending on NRLs. Consensus clustering method and the risk scoring system were basically similar. Survival probability was higher in Cluster 2, while Cluster 1 has stronger immunologic infiltration.

CONCLUSION

The predictive signature could be a prognostic factor independently and serve to detect the role of NRLs in glioma immunotherapy response.

摘要

背景

在肿瘤进展和表观遗传调控中，长链非编码 RNA（lncRNA）和坏死性凋亡是关键的调节因子。然而，在神经胶质瘤微环境中，坏死性凋亡相关 lncRNA（NRL）的作用仍不清楚。

方法

本研究利用癌症基因组图谱（TCGA）和中国神经胶质瘤基因组图谱（CGGA）数据库分析了神经胶质瘤患者的 RNA-seq 和临床注释。为了研究 NRL 在神经胶质瘤中的预后和肿瘤微环境作用，我们基于训练队列构建了一个预测模型，并在验证队列中验证了该模型的准确性。

结果

鉴定了由 13 个 NRL 组成的特征，并将所有神经胶质瘤患者分为两组。我们发现每组都有独特的生存结局、生物学行为和免疫浸润状态。坏死性凋亡相关 lncRNA 特征（NRLS）模型在多变量 Cox 分析中是一个独立的危险因素。免疫抑制性微环境与高危组呈正相关。由于风险组之间的 IC50 存在显著差异，NRLS 可作为化疗治疗的指导。此外，根据 NRL 将整个队列分为两个簇。共识聚类方法和风险评分系统基本相似。Cluster 2 的生存概率更高，而 Cluster 1 具有更强的免疫浸润。