DNA methylation heterogeneity attributable to a complex tumor immune microenvironment prompts prognostic risk in glioma

Shuangyue Ma; Xu Pan; Jing Gan; Xiaxin Guo; Jiaheng He; Haoyu Hu; Yuncong Wang; Shangwei Ning; Hui Zhi

doi:10.1080/15592294.2024.2318506

Epigenetics (Dec 2024)

DNA methylation heterogeneity attributable to a complex tumor immune microenvironment prompts prognostic risk in glioma

Shuangyue Ma,
Xu Pan,
Jing Gan,
Xiaxin Guo,
Jiaheng He,
Haoyu Hu,
Yuncong Wang,
Shangwei Ning,
Hui Zhi

Affiliations

Shuangyue Ma: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China
Xu Pan: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China
Jing Gan: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China
Xiaxin Guo: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China
Jiaheng He: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China
Haoyu Hu: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China
Yuncong Wang: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China
Shangwei Ning: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China
Hui Zhi: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China

DOI: https://doi.org/10.1080/15592294.2024.2318506
Journal volume & issue: Vol. 19, no. 1

Abstract

Read online

ABSTRACTGliomas are malignant tumours of the human nervous system with different World Health Organization (WHO) classifications, glioblastoma (GBM) with higher grade and are more malignant than lower-grade glioma (LGG). To dissect how the DNA methylation heterogeneity in gliomas is influenced by the complex cellular composition of the tumour immune microenvironment, we first compared the DNA methylation profiles of purified human immune cells and bulk glioma tissue, stratifying three tumour immune microenvironmental subtypes for GBM and LGG samples from The Cancer Genome Atlas (TCGA). We found that more intermediate methylation sites were enriched in glioma tumour tissues, and used the Proportion of sites with Intermediate Methylation (PIM) to compare intertumoral DNA methylation heterogeneity. A larger PIM score reflected stronger DNA methylation heterogeneity. Enhanced DNA methylation heterogeneity was associated with stronger immune cell infiltration, better survival rates, and slower tumour progression in glioma patients. We then created a Cell-type-associated DNA Methylation Heterogeneity Contribution (CMHC) score to explore the impact of different immune cell types on heterogeneous CpG site (CpGct) in glioma tissues. We identified eight prognosis-related CpGct to construct a risk score: the Cell-type-associated DNA Methylation Heterogeneity Risk (CMHR) score. CMHR was positively correlated with cytotoxic T-lymphocyte infiltration (CTL), and showed better predictive performance for IDH status (AUC = 0.96) and glioma histological phenotype (AUC = 0.81). Furthermore, DNA methylation alterations of eight CpGct might be related to drug treatments of gliomas. In conclusion, we indicated that DNA methylation heterogeneity is associated with a complex tumour immune microenvironment, glioma phenotype, and patient’s prognosis.

Published in Epigenetics

ISSN: 1559-2294 (Print); 1559-2308 (Online)
Publisher: Taylor & Francis Group
Country of publisher: United Kingdom
LCC subjects: Science: Biology (General): Genetics
Website: https://www.tandfonline.com/kepi

About the journal

Abstract

Keywords