Redox Regulator GLRX Is Associated With Tumor Immunity in Glioma.
Redox Regulator GLRX Is Associated With Tumor Immunity in Glioma.
复制标题
氧化还原调节剂 GLRX 与神经胶质瘤的肿瘤免疫相关。
DOI：
10.3389/fimmu.2020.580934
复制
发表时间：
2020
影响因子：
7.3
通讯作者：
Hu H
中科院分区：
文献类型：
--
作者：
Chang Y;Li G;Zhai Y;Huang L;Feng Y;Wang D;Zhang W;Hu H
谷氧还蛋白是细胞氧化还原化学的中心，调节氧化还原动态平衡和许多癌症的恶性进展。在胶质瘤中，其编码基因(GLRX)的作用尚不清楚。我们的目的是阐明谷氧还蛋白在转录组水平上的作用及其在胶质瘤中的临床预后价值。我们总共评估了1717个胶质瘤样本，包括转录组数据和相应的临床数据，以及来自公开数据库的6名胶质瘤患者的单细胞测序数据。通过基因集变异分析和基因本体论分析揭示GLRX的生物学功能。GSVA分析计算免疫细胞浓缩评分。单细胞测序数据采用t分布随机邻域嵌入分析进行可视化处理。Kaplan-Meier曲线和多因素Cox分析证实了GLRX在脑胶质瘤中的预后价值。GLRX在具有野生型IDH、无1p/19q共缺失和带有甲基化MGMT启动子的高级别胶质瘤中高度富含。此外，GLRX可能是脑胶质瘤间充质分子亚型的一个潜在标记物。GLRX的表达与肿瘤免疫过程、免疫检查点和炎症因子密切相关，其中GLRX在M0巨噬细胞中特异表达。GLRX也被证明是胶质瘤的一个独立的预后因素。总之，我们的研究结果表明，GLRX在恶性胶质瘤中高度丰富，并与肿瘤免疫微环境密切相关。因此，GLRX靶向细胞氧化还原调节治疗可能会增强胶质瘤免疫治疗的疗效。
Glutaredoxin is central to cellular redox chemistry and regulates redox homeostasis and malignant progression of many cancers. In glioma, the role of its coding gene (GLRX) remains unclear. We aimed to elucidate the role of glutaredoxin at the transcriptome level and its clinical prognostic value in glioma. In total, we evaluated 1,717 glioma samples with transcriptome data and corresponding clinical data as well as single-cell sequencing data from 6 glioma patients from publicly available databases. Gene set variation analysis and gene ontology analysis were performed to reveal the biological function of GLRX. The immune cell enrichment score was calculated by GSVA analysis. Single-cell sequencing data was visualized by t-distributed stochastic neighbor embedding analysis. The prognostic value of GLRX in glioma was verified by the Kaplan-Meier curve and multivariate COX analysis. GLRX was found to be highly enriched in gliomas of higher grades with wild-type IDH, without 1p/19q co-deletion, and with a methylated MGMT promoter. Moreover, GLRX could be a potential marker for the mesenchymal molecular subtype of gliomas. The expression of GLRX was closely related to the tumor immune process, immune checkpoints, and inflammatory factors with GLRX being specifically expressed in M0 macrophages. GLRX is also shown to be an independent prognostic factor in glioma. Altogether, our study outcomes show that GLRX is highly enriched in malignant gliomas and is closely related to the tumor immune microenvironment. Therefore, GLRX-targeted cell redox regulatory therapy may enhance the efficacy of glioma immunotherapy.