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="https://fatcat.wiki/container/mefn5t5kjndavkrqau5bzfpaoe" 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="https://doi.org/10.3389/fonc.2020.541401">doi:10.3389/fonc.2020.541401</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/33123464">pmid:33123464</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC7571468/">pmcid:PMC7571468</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/fmrz4erkvjh2fmkvm6uavvlvya">fatcat:fmrz4erkvjh2fmkvm6uavvlvya</a> </span>
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