<i>PODNL1</i> Methylation Serves as a Prognostic Biomarker and Associates with Immune Cell Infiltration and Immune Checkpoint Blockade Response in Lower-Grade Glioma
Lower-grade glioma (LGG) is a diffuse infiltrative tumor of the central nervous system, which lacks targeted therapy. We investigated the role of <i>Podocan-like 1</i> (<i>PODNL1</i>) methylation in LGG clinical outcomes using the TCGA-LGG transcriptomics dataset. We identifi...
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| Auteurs principaux: | , , , |
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| Format: | article |
| Langue: | EN |
| Publié: |
MDPI AG
2021
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| Sujets: | |
| Accès en ligne: | https://doaj.org/article/1b67eb37d64f4c73b3ab3413e52d954c |
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| Résumé: | Lower-grade glioma (LGG) is a diffuse infiltrative tumor of the central nervous system, which lacks targeted therapy. We investigated the role of <i>Podocan-like 1</i> (<i>PODNL1</i>) methylation in LGG clinical outcomes using the TCGA-LGG transcriptomics dataset. We identified four <i>PODNL1</i> CpG sites, cg07425555, cg26969888, cg18547299, and cg24354933, which were associated with unfavorable overall survival (OS) and disease-free survival (DFS) in univariate and multivariate analysis after adjusting for age, gender, tumor-grade, and <i>IDH1</i>-mutation. In multivariate analysis, the OS and DFS hazard ratios ranged from 0.44 to 0.58 (<i>p</i> < 0.001) and 0.62 to 0.72 (<i>p</i> < 0.001), respectively, for the four <i>PODNL1</i> CpGs. Enrichment analysis of differential gene and protein expression and analysis of 24 infiltrating immune cell types showed significantly increased infiltration in LGGs and its histological subtypes with low-methylation levels of the <i>PODNL1</i> CpGs. High <i>PODNL1</i> expression and low-methylation subgroups of the <i>PODNL1</i> CpG sites were associated with significantly increased <i>PD-L1, PD-1</i>, and <i>CTLA4</i> expressions. <i>PODNL1</i> methylation may thus be a potential indicator of immune checkpoint blockade response, and serve as a biomarker for determining prognosis and immune subtypes in LGG. |
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