miR-17-5p-CXCL14 axis related transcriptome profile and clinical outcome in diffuse gliomas
miR-17-5p-CXCL14 axis related transcriptome profile and clinical outcome in diffuse gliomas
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弥漫性胶质瘤中 miR-17-5p-CXCL14 轴相关的转录组谱和临床结果。
DOI：
10.1080/2162402x.2018.1510277
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发表时间：
2018-12-02
期刊：
影响因子：
7.2
通讯作者：
You, Yongping
中科院分区：
文献类型：
--
作者：
Zeng, Ailiang;Yin, Jianxin;You, Yongping
GBM组织不仅由肿瘤细胞组成，还包括肿瘤相关的非肿瘤细胞，如基质细胞和免疫细胞，其稀释了胶质瘤细胞的纯度并在胶质瘤生物学中起作用。然而，miRNAs在调节胶质瘤纯度中的作用并不明确。本研究共收集了838例具有转录组数据的胶质瘤样本，其中包括537例来自TCGA项目的RNAseq数据和301例来自中国胶质瘤基因组图谱（CGGA项目）的微阵列数据。肿瘤纯度、分子亚型和IDH状态也可用。采用R语言作为统计分析和图形工作的主要工具。筛选miRNA谱和配对TCGA样本的转录组数据表明，在所有miRNA中，miR-17- 5 p表达与胶质瘤纯度具有最显著的正相关性。在TCGA和CGGA数据集中，CXCL 14显示与miR-17- 5 p表达的稳健负相关性。miR-17- 5 p直接靶向CXCL 14并作为GBM的肿瘤抑制因子发挥作用。CXCL 14在前神经亚型中表达较低，可能是胶质瘤前神经亚型的潜在标志物。与CXCL 14显著相关的基因参与了与抗肿瘤免疫过程相关的重要功能。CXCL 14与胶质瘤环境中的免疫（T细胞、单核细胞谱系和中性粒细胞）和成纤维细胞具有强相关性。miR-17- 5 p和CXCL 14对高级别胶质瘤（HGG）患者具有预测价值：较高的miR-17- 5 p表明生存期显著延长，而较低的CXCL 14表明生存期延长。我们的研究结果强调了miR-17- 5 p-CXCL 14轴在调节抗肿瘤免疫过程的关键步骤中的重要性，并可能作为胶质瘤免疫治疗的潜在靶点。
GBM tissues are comprised of not only tumor cells but also tumor-associated nontumor cells, such as stromal cells and immune cells, which dilute the purity of glioma cells and function in glioma biology. However, the roles of miRNAs in modulating glioma purity are not clari?ed. In total, 838 glioma samples with transcriptome data, including 537 RNAseq data from TCGA project and 301 microarray data from Chinese Glioma Genome Atlas (CGGA project), were recruited into our investigation. Tumor purity, molecular subtypes and IDH status were also available. R language was employed as the main tool for statistical analysis and graphical work. Screening miRNA profiling and paired TCGA samples' transcriptome data demonstrates that miR-17-5p expression harbors the most significant positive correlation with glioma purity among all miRNAs. CXCL14 shows robust negative correlation with miR-17-5p expression in TCGA and CGGA dataset. miR-17-5p directly targets CXCL14 and functions as a tumor-suppressor of GBM. CXCL14 showed lower expression in proneural subtype and may contribute as a potential marker for proneural subtype in glioma. Genes markedly correlated with CXCL14 are involved in essential functions associated with anti-tumor immune process. CXCL14 has a strong correlation with immune(T cells, Monocytic lineage and Neutrophils) and Fibroblasts within glioma environment. miR-17-5p and CXCL14 exhibited predictive values for high-grade glioma(HGG) patients: Higher miR-17-5p indicated significantly longer survival while lower CXCL14 indicated longer survival. Our results highlight the importance of the miR-17-5p-CXCL14 axis in regulating key steps of anti-tumor immune process and may serve as potential targets of immune treatments for gliomas.