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鉴定胶质母细胞瘤患者上皮-间充质转化相关长非编码 RNA 预后特征。

Identification of an epithelial-mesenchymal transition-related lncRNA prognostic signature for patients with glioblastoma.

机构信息

Department of Neurosurgery, The Translational Research Institute for Neurological Disorders, the First Affiliated Hospital (Yijishan Hospital), Wannan Medical College, Wuhu, Anhui, China.

Department of Neurosurgery, the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital), Wannan Medical College, Wuhu, Anhui, China.

出版信息

Sci Rep. 2021 Dec 8;11(1):23694. doi: 10.1038/s41598-021-03213-y.

Abstract

Glioblastoma (GBM) is a strikingly heterogeneous and lethal brain tumor with very poor prognosis. LncRNAs play critical roles in the tumorigenesis of GBM through regulation of various cancer-related genes and signaling pathways. Here, we focused on the essential role of EMT and identified 78 upregulated EMT-related genes in GBM through differential expression analysis and Gene set enrichment analysis (GSEA). A total of 301 EMT-related lncRNAs were confirmed in GBM through Spearman correlation analysis and a prognostic signature consisting of seven EMT-related lncRNAs (AC012615.1, H19, LINC00609, LINC00634, POM121L9P, SNHG11, and USP32P3) was established by univariate and multivariate Cox regression analyses. Significantly, Kaplan-Meier analysis and receiver-operating-characteristic (ROC) curve validated the accuracy and efficiency of the signature to be satisfactory. Quantitative real-time (qRT)-PCR assay demonstrated the expression alterations of the seven lncRNAs between normal glial and glioma cell lines. Functional enrichment analysis revealed multiple EMT and metastasis-related pathways were associated with the EMT-related lncRNA prognostic signature. In addition, we observed the degree of immune cell infiltration and immune responses were significantly increased in high-risk subgroup compared with low-risk subgroup. In conclusion, we established an effective and robust EMT-related lncRNA signature which was expected to predict the prognosis and immunotherapy response for GBM patients.

摘要

胶质母细胞瘤(GBM)是一种明显异质性和致命的脑肿瘤,预后极差。LncRNAs 通过调节各种癌症相关基因和信号通路,在 GBM 的肿瘤发生中发挥关键作用。在这里,我们重点研究了 EMT 的重要作用,并通过差异表达分析和基因集富集分析(GSEA)确定了 GBM 中 78 个上调的 EMT 相关基因。通过 Spearman 相关性分析和单变量和多变量 Cox 回归分析,总共在 GBM 中确认了 301 个 EMT 相关 lncRNAs,建立了一个由七个 EMT 相关 lncRNAs(AC012615.1、H19、LINC00609、LINC00634、POM121L9P、SNHG11 和 USP32P3)组成的预后特征。显著的 Kaplan-Meier 分析和接收器操作特征(ROC)曲线验证了该特征的准确性和效率令人满意。定量实时(qRT)-PCR 检测证实了这七个 lncRNAs 在正常神经胶质和神经胶质瘤细胞系之间的表达变化。功能富集分析显示,多个 EMT 和转移相关途径与 EMT 相关 lncRNA 预后特征相关。此外,我们观察到高风险亚组的免疫细胞浸润和免疫反应程度明显高于低风险亚组。总之,我们建立了一个有效的、稳健的 EMT 相关 lncRNA 特征,有望预测 GBM 患者的预后和免疫治疗反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfd5/8654911/9f500d6f7fce/41598_2021_3213_Fig1_HTML.jpg

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