Gao Ming, Wang Xinzhuang, Han Dayong, Lu Enzhou, Zhang Jian, Zhang Cheng, Wang Ligang, Yang Quan, Jiang Qiuyi, Wu Jianing, Chen Xin, Zhao Shiguang
Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China.
Front Genet. 2021 Jan 13;11:604655. doi: 10.3389/fgene.2020.604655. eCollection 2020.
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.
多形性胶质母细胞瘤(GBM)是中枢神经系统中最具侵袭性的原发性肿瘤。随着生物医学的发展,研究人员发现GBM的发展与免疫密切相关。在本研究中,我们基于五个免疫表达特征(IFN-γ反应、巨噬细胞、淋巴细胞浸润、TGF-β反应和伤口愈合)的单样本基因集富集分析(ssGSEA),使用来自癌症基因组图谱(TCGA)项目分析的144个肿瘤的转录组数据,评估了GBM肿瘤免疫反应性,并定义了免疫高(IH)和免疫低(IL)免疫表型。接下来,我们通过采用结合最小冗余最大相关性算法(mRMR)和随机森林模型的机器学习计算框架,鉴定了六个与免疫表型相关的长链非编码RNA生物标志物(im-lncRNAs,USP30-AS1、HCP5、PSMB8-AS1、AL133264.2、LINC01684和LINC01506)。此外,使用标准化主成分分析将鉴定出的im-lncRNAs的表达水平转换为im-lncScore。im-lncScore在区分GBM免疫表型方面表现出良好的性能,曲线下面积(AUC)为0.928。此外,im-lncRNAs也与GBM中肿瘤免疫细胞浸润水平密切相关。总之,im-lncRNA特征对未来胶质母细胞瘤患者的肿瘤免疫表型分析和指导免疫治疗具有重要的临床意义。