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Redox Regulator GLRX Is Associated With Tumor Immunity in Glioma
Frontiers in Immunology ( IF 5.7 ) Pub Date : 2020-10-26 , DOI: 10.3389/fimmu.2020.580934
Yuanhao Chang 1 , Guanzhang Li 1 , You Zhai 1 , Lijie Huang 1 , Yuemei Feng 1 , Di Wang 2 , Wei Zhang 2, 3, 4 , Huimin Hu 1, 4
Affiliation  

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.



中文翻译:

氧化还原调节剂GLRX与胶质瘤的肿瘤免疫相关。

谷胱甘肽毒素是细胞氧化还原化学的核心,调节许多癌症的氧化还原稳态和恶性进展。在神经胶质瘤中,其编码基因的作用(GLRX) 还不清楚。我们的目的是阐明谷胱甘肽在转录组水平上的作用及其在神经胶质瘤中的临床预后价值。我们总共评估了1,717个神经胶质瘤样本,其中包含转录组数据和相应的临床数据,以及来自公开数据库的6个神经胶质瘤患者的单细胞测序数据。进行基因组变异分析和基因本体分析以揭示其生物学功能。GLRX。通过GSVA分析计算免疫细胞富集得分。单细胞测序数据通过Ť分布随机邻居嵌入分析。的预后价值GLRX 通过Kaplan-Meier曲线和多元COX分析验证了神经胶质瘤中的肿瘤。 GLRX 被发现在野生型高等级神经胶质瘤中高度富集 IDH,无需1p / 19q共删除,并带有甲基化 MGMT启动子。此外,GLRX可能是神经胶质瘤间质分子亚型的潜在标志。表达GLRX 与肿瘤的免疫过程,免疫检查点和炎症因子密切相关 GLRX 在M0巨噬细胞中特异性表达。 GLRX也被证明是神经胶质瘤的独立预后因素。总而言之,我们的研究结果表明GLRX高度富含恶性神经胶质瘤,与肿瘤免疫微环境密切相关。因此,GLRX靶向的细胞氧化还原调节疗法可增强神经胶质瘤免疫疗法的疗效。

更新日期:2020-12-01
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