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RELB:基于人群分析确定的胶质母细胞瘤新型预后标志物。

RELB: A novel prognostic marker for glioblastoma as identified by population-based analysis.

作者信息

Zeng Fan, Wang Kuanyu, Huang Ruoyu, Liu Yanwei, Zhang Ying, Hu Huimin

机构信息

Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, P.R. China.

Chinese Glioma Cooperative Group (CGCG), Beijing 100070, P.R. China.

出版信息

Oncol Lett. 2019 Jul;18(1):386-394. doi: 10.3892/ol.2019.10296. Epub 2019 Apr 30.

Abstract

Glioblastoma multiforme (GBM) is the most common and malignant type of glioma, with a poor prognosis for patients. The survival time of patients varies greatly due to the complexity of the human genome, which harbors diverse oncogenic drivers. In order to identify the specific driving factors, 325 glioma samples from the Chinese Glioma Genome Atlas (CGGA) database were analyzed in the present study. The level of RELB proto-oncogene, NF-κβ subunit (RELB) expression increased with the pathological grade progression of the gliomas, and higher expression levels were present in the mesenchymal subtype and isocitrate dehydrogenase 1 (IDH1) wild-type gliomas. This RELB expression pattern was identified in the CGGA database and observed in three large independent databases. In patients with GBM from the CGGA database, a higher RELB expression level was associated with a shorter survival time, a mesenchymal subtype and IDH1 wild-type gliomas. Kaplan-Meier survival analysis, survival nomograms and Cox analysis demonstrated an independent prognostic value for RELB expression. Moreover, biological function analysis indicated the association of RELB with the 'immune response', 'cell activation' and the 'apoptotic process'. In addition, RELB expression levels exhibited a negative correlation with the levels of microRNA (miR)-139-5p and miR-139-3p. The present study identified the pathological and biological roles of RELB in glioma and revealed its independent prognostic effect. These results suggested that RELB may be used as a prognostic biomarker and potential therapeutic target in glioma.

摘要

多形性胶质母细胞瘤(GBM)是最常见且恶性程度最高的胶质瘤类型,患者预后较差。由于人类基因组的复杂性,其中包含多种致癌驱动因素,患者的生存时间差异很大。为了确定具体的驱动因素,本研究分析了来自中国胶质瘤基因组图谱(CGGA)数据库的325个胶质瘤样本。原癌基因RELB、NF-κβ亚基(RELB)的表达水平随着胶质瘤病理分级的进展而升高,在间充质亚型和异柠檬酸脱氢酶1(IDH1)野生型胶质瘤中表达水平更高。这种RELB表达模式在CGGA数据库中得到确认,并在三个大型独立数据库中观察到。在CGGA数据库的GBM患者中,较高的RELB表达水平与较短的生存时间、间充质亚型和IDH1野生型胶质瘤相关。Kaplan-Meier生存分析、生存列线图和Cox分析表明RELB表达具有独立的预后价值。此外,生物学功能分析表明RELB与“免疫反应”、“细胞活化”和“凋亡过程”有关。此外,RELB表达水平与微小RNA(miR)-139-5p和miR-139-3p的水平呈负相关。本研究确定了RELB在胶质瘤中的病理和生物学作用,并揭示了其独立的预后作用。这些结果表明,RELB可能作为胶质瘤的预后生物标志物和潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e0f/6540354/ce7a58bb29dd/ol-18-01-0386-g00.jpg

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