Dataset Information

PODNL1 Methylation Serves as a Prognostic Biomarker and Associates with Immune Cell Infiltration and Immune Checkpoint Blockade Response in Lower-Grade Glioma.

ABSTRACT: 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.

SUBMITTER: Noor H

PROVIDER: S-EPMC8625785 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundThe CKLF-like MARVEL transmembrane domain-containing 3 (CMTM3) is differentially expressed in a variety of tumors and closely related to tumor occurrence and progression. The expression of CMTM3 was significantly elevated in glioma compared with normal brain tissue, to explore the potential function of CMTM3 in the prognosis and immune infiltration of glioma has certain clinical significance.MethodsThe tumor data in this study were derived from the sequencing data of various tumors in The Cancer Genome Atlas (TCGA) database. Low-grade glioma (LGG) data in the TCGA database include sequencing and clinical data. Clinical data mainly include survival time, survival outcome, age, WHO classification and other information. Sequencing data for normal tissues were obtained from the Genotype Tissue Expression (GTEx) database. Statistical analyses were mainly performed using bioinformatics tools and the corresponding R software (version 3.6.3). The Mann-Whitney U test (Wilcoxon rank sum test) was used to compare the expression differences between the tumor group and the normal group. Survival analysis was conducted using log-rank test to compare whether the overall survival (OS) time was statistically different between the CMTM3 high and low expression groups. The Tumor Immunity Estimation Resource (TIMER) database was used for immune infiltration analysis.ResultsThe results showed that the expression of CMTM3 in World Health Organization (WHO) II and WHO III gliomas was significantly higher than that of normal tissues (P<0.05). Glioma with high CMTM3 expression showed a lower overall survival (OS) (P<0.05). Gene enrichment analysis showed that CMTM3 was significantly enriched in 4 pathways (FDR <0.25, P<0.05). A high correlation was detected between CMTM3 and a variety of immune cells. CMTM3 is highly correlated with macrophages (r=0.536, P=1.31e-36), dendritic cells (r=0.546, P=2.85e-38), CD4+ T cells (r=0.517, P=6.17e-34).ConclusionsThe CMTM3 gene can be used as a potential prognostic marker for WHO grade II and WHO grade III glioma, is related to the immune infiltration in glioma microenvironment, and may became a new immunotherapy target.

Dataset Information

PODNL1 Methylation Serves as a Prognostic Biomarker and Associates with Immune Cell Infiltration and Immune Checkpoint Blockade Response in Lower-Grade Glioma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets