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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 identified four PODNL1 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 IDH1-mutation. In multivariate analysis, the OS and DFS hazard ratios ranged from 0.44 to 0.58 (p < 0.001) and 0.62 to 0.72 (p < 0.001), respectively, for the four PODNL1 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 PODNL1 CpGs. High PODNL1 expression and low-methylation subgroups of the PODNL1 CpG sites were associated with significantly increased PD-L1, PD-1, and CTLA4 expressions. PODNL1 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.

Type Journal
ISBN 1422-0067 (Electronic) 1422-0067 (Linking)
Authors Noor, H.; Zaman, A.; Teo, C.; Sughrue, M. E.
Responsible Garvan Author Dr Ashraf Zaman
Published Date 2021-11-30
Published Volume 22
Published Issue 22
Published Pages 12572
Status Published in-print
DOI 10.3390/ijms222212572
URL link to publisher's version