Prognosis Analysis and Validation of m6A Signature and Tumor Immune Microenvironment in Glioma

Shaojian Lin, Houshi Xu, Anke Zhang, Yunjia Ni, Yuanzhi Xu, Tong Meng, Mingjie Wang, Meiqing Lou
<span title="2020-10-05">2020</span> <i title="Frontiers Media SA"> <a target="_blank" rel="noopener" href="" style="color: black;">Frontiers in Oncology</a> </i> &nbsp;
Glioma is one of the most typical intracranial tumors, comprising about 80% of all brain malignancies. Several key molecular signatures have emerged as prognostic biomarkers, which indicate room for improvement in the current approach to glioma classification. In order to construct a more veracious prediction model and identify the potential prognosis-biomarker, we explore the differential expressed m6A RNA methylation regulators in 665 gliomas from TCGA-GBM and TCGA-LGG. Consensus clustering
more &raquo; ... s applied to the m6A RNA methylation regulators, and two glioma subgroups were identified with a poorer prognosis and a higher grade of WHO classification in cluster 1. The further chi-squared test indicated that the immune infiltration was significantly enriched in cluster 1, indicating a close relation between m6A regulators and immune infiltration. In order to explore the potential biomarkers, the weighted gene co-expression network analysis (WGCNA), along with Least absolute shrinkage and selection operator (LASSO), between high/low immune infiltration and m6A cluster 1/2 groups were utilized for the hub genes, and four genes (TAGLN2, PDPN, TIMP1, EMP3) were identified as prognostic biomarkers. Besides, a prognostic model was constructed based on the four genes with a good prediction and applicability for the overall survival (OS) of glioma patients (the area under the curve of ROC achieved 0.80 (0.76-0.83) and 0.72 (0.68-0.76) in TCGA and Chinese Glioma Genome Atlas (CGGA), respectively). Moreover, we also found PDPN and TIMP1 were highly expressed in high-grade glioma from The Human Protein Atlas database and both of them were correlated with m6A and immune cell marker in glioma tissue samples. In conclusion, we construct a novel prognostic model which provides new insights into glioma prognosis. The PDPN and TIMP1 may serve as potential biomarkers for prognosis of glioma.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="">doi:10.3389/fonc.2020.541401</a> <a target="_blank" rel="external noopener" href="">pmid:33123464</a> <a target="_blank" rel="external noopener" href="">pmcid:PMC7571468</a> <a target="_blank" rel="external noopener" href="">fatcat:fmrz4erkvjh2fmkvm6uavvlvya</a> </span>
<a target="_blank" rel="noopener" href=";sr=b&amp;sig=winqxaca3aFK%2FnVVf4u9sMrqN8zlTP5U9q2nzFrhoGU%3D&amp;se=2020-10-06T05%3A28%3A59Z&amp;sp=r&amp;rscd=attachment%3B%20filename%2A%3DUTF-8%27%27fonc-10-541401.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href=""> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="unlock alternate icon" style="background-color: #fb971f;"></i> </button> </a> <a target="_blank" rel="external noopener" href="" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> </button> </a>