AUTHOR=Chang Yuanhao , Li Guanzhang , Zhai You , Huang Lijie , Feng Yuemei , Wang Di , Zhang Wei , Hu Huimin 

TITLE=Redox Regulator GLRX Is Associated With Tumor Immunity in Glioma

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.580934

DOI=10.3389/fimmu.2020.580934

ISSN=1664-3224

ABSTRACT=<p>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 (<italic>GLRX</italic>) 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 <italic>GLRX</italic>. The immune cell enrichment score was calculated by GSVA analysis. Single-cell sequencing data was visualized by <italic>t</italic>-distributed stochastic neighbor embedding analysis. The prognostic value of <italic>GLRX</italic> in glioma was verified by the Kaplan-Meier curve and multivariate COX analysis. <italic>GLRX</italic> was found to be highly enriched in gliomas of higher grades with wild-type <italic>IDH</italic>, without 1p/19q co-deletion, and with a methylated <italic>MGMT</italic> promoter. Moreover, <italic>GLRX</italic> could be a potential marker for the mesenchymal molecular subtype of gliomas. The expression of <italic>GLRX</italic> was closely related to the tumor immune process, immune checkpoints, and inflammatory factors with <italic>GLRX</italic> being specifically expressed in M0 macrophages. <italic>GLRX</italic> is also shown to be an independent prognostic factor in glioma. Altogether, our study outcomes show that <italic>GLRX</italic> is highly enriched in malignant gliomas and is closely related to the tumor immune microenvironment. Therefore, <italic>GLRX</italic>-targeted cell redox regulatory therapy may enhance the efficacy of glioma immunotherapy.</p>