PODNL1 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 Podocan-like 1 (PODNL1) methylation in LGG clinical outcomes using the TCGA-LGG transcriptomics dataset. We identifi...

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Autores principales:	Humaira Noor, Ashraf Zaman, Charles Teo, Michael E. Sughrue
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>Podocan-like 1</i> <i>PODNL1</i> glioma low-grade glioma CpG methylation G-CIMP Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/1b67eb37d64f4c73b3ab3413e52d954c
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spelling	oai:doaj.org-article:1b67eb37d64f4c73b3ab3413e52d954c2021-11-25T17:57:59Z<i>PODNL1</i> Methylation Serves as a Prognostic Biomarker and Associates with Immune Cell Infiltration and Immune Checkpoint Blockade Response in Lower-Grade Glioma10.3390/ijms2222125721422-00671661-6596https://doaj.org/article/1b67eb37d64f4c73b3ab3413e52d954c2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12572https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Lower-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.Humaira NoorAshraf ZamanCharles TeoMichael E. SughrueMDPI AGarticle<i>Podocan-like 1</i><i>PODNL1</i>gliomalow-grade gliomaCpG methylationG-CIMPBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12572, p 12572 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Podocan-like 1</i> <i>PODNL1</i> glioma low-grade glioma CpG methylation G-CIMP Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	<i>Podocan-like 1</i> <i>PODNL1</i> glioma low-grade glioma CpG methylation G-CIMP Biology (General) QH301-705.5 Chemistry QD1-999 Humaira Noor Ashraf Zaman Charles Teo Michael E. Sughrue <i>PODNL1</i> Methylation Serves as a Prognostic Biomarker and Associates with Immune Cell Infiltration and Immune Checkpoint Blockade Response in Lower-Grade Glioma
description	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.
format	article
author	Humaira Noor Ashraf Zaman Charles Teo Michael E. Sughrue
author_facet	Humaira Noor Ashraf Zaman Charles Teo Michael E. Sughrue
author_sort	Humaira Noor
title	<i>PODNL1</i> Methylation Serves as a Prognostic Biomarker and Associates with Immune Cell Infiltration and Immune Checkpoint Blockade Response in Lower-Grade Glioma
title_short	<i>PODNL1</i> Methylation Serves as a Prognostic Biomarker and Associates with Immune Cell Infiltration and Immune Checkpoint Blockade Response in Lower-Grade Glioma
title_full	<i>PODNL1</i> Methylation Serves as a Prognostic Biomarker and Associates with Immune Cell Infiltration and Immune Checkpoint Blockade Response in Lower-Grade Glioma
title_fullStr	<i>PODNL1</i> Methylation Serves as a Prognostic Biomarker and Associates with Immune Cell Infiltration and Immune Checkpoint Blockade Response in Lower-Grade Glioma
title_full_unstemmed	<i>PODNL1</i> Methylation Serves as a Prognostic Biomarker and Associates with Immune Cell Infiltration and Immune Checkpoint Blockade Response in Lower-Grade Glioma
title_sort	<i>podnl1</i> methylation serves as a prognostic biomarker and associates with immune cell infiltration and immune checkpoint blockade response in lower-grade glioma
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/1b67eb37d64f4c73b3ab3413e52d954c
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<i>PODNL1</i> Methylation Serves as a Prognostic Biomarker and Associates with Immune Cell Infiltration and Immune Checkpoint Blockade Response in Lower-Grade Glioma

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