A Six-lncRNA Signature for Immunophenotype Prediction of Glioblastoma Multiforme.

A Six-lncRNA Signature for Immunophenotype Prediction of Glioblastoma Multiforme.
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DOI:
10.3389/fgene.2020.604655
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发表时间:
2020
影响因子:
3.7
通讯作者:
Zhao S
Zhao S
中科院分区:
生物学3区
文献类型:
--
作者:
Gao M;Wang X;Han D;Lu E;Zhang J;Zhang C;Wang L;Yang Q;Jiang Q;Wu J;Chen X;Zhao S

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多形性胶质母细胞瘤(GBM)是中枢神经系统最具侵袭性的原发肿瘤。随着生物医学的发展,研究者发现GBM的发生与免疫密切相关。在这项研究中,我们利用144个肿瘤的转录组数据评估了GBM肿瘤的免疫反应性,并根据五种免疫表达特征(IFN-γ应答、巨噬细胞、淋巴细胞浸润、TGF-β应答和伤口愈合)的单样本基因集富集分析(ssGSEA),利用癌症基因组图谱(TCGA)项目描述的144个肿瘤的转录组数据定义了免疫高(IH)和免疫低(IL)免疫表型。接下来,我们利用结合最小冗余最大相关算法(mRMR)和随机森林模型的机器学习计算框架,鉴定了6个与免疫表型相关的长链非编码RNA生物标志物(m - lncrnas、USP30-AS1、HCP5、PSMB8-AS1、AL133264.2、LINC01684和LINC01506)。此外,使用归一化主成分分析将鉴定出的im- lncrna的表达水平转换为im- lncrna得分。im-lncScore在鉴别GBM免疫表型方面表现良好,曲线下面积(AUC)为0.928。此外,im- lncrna还与GBM中肿瘤免疫细胞浸润水平密切相关。综上所述,im-lncRNA标记对未来胶质母细胞瘤患者的肿瘤免疫分型和指导免疫治疗具有重要的临床意义。
Glioblastoma multiforme (GBM) is the most aggressive primary tumor of the central nervous system. As biomedicine advances, the researcher has found the development of GBM is closely related to immunity. In this study, we evaluated the GBM tumor immunoreactivity and defined the Immune-High (IH) and Immune-Low (IL) immunophenotypes using transcriptome data from 144 tumors profiled by The Cancer Genome Atlas (TCGA) project based on the single-sample gene set enrichment analysis (ssGSEA) of five immune expression signatures (IFN-γ response, macrophages, lymphocyte infiltration, TGF-β response, and wound healing). Next, we identified six immunophenotype-related long non-coding RNA biomarkers (im-lncRNAs, USP30-AS1, HCP5, PSMB8-AS1, AL133264.2, LINC01684, and LINC01506) by employing a machine learning computational framework combining minimum redundancy maximum relevance algorithm (mRMR) and random forest model. Moreover, the expression level of identified im-lncRNAs was converted into an im-lncScore using the normalized principal component analysis. The im-lncScore showed a promising performance for distinguishing the GBM immunophenotypes with an area under the curve (AUC) of 0.928. Furthermore, the im-lncRNAs were also closely associated with the levels of tumor immune cell infiltration in GBM. In summary, the im-lncRNA signature had important clinical implications for tumor immunophenotyping and guiding immunotherapy in glioblastoma patients in future.
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