Regulatory pattern of abnormal promoter CpG island methylation in the glioblastoma multiforme classification

Rendong Wang; Lei Zhao; Shijia Wang; Xiaoxiao Zhao; Chuanyu Liang; Pei Wang; Dongguo Li

doi:10.3389/fgene.2022.989985

Regulatory pattern of abnormal promoter CpG island methylation in the glioblastoma multiforme classification

Front Genet. 2022 Sep 19:13:989985. doi: 10.3389/fgene.2022.989985. eCollection 2022.

Authors

Rendong Wang^{1

2}, Lei Zhao³, Shijia Wang^{1

2}, Xiaoxiao Zhao^{1

2}, Chuanyu Liang³, Pei Wang³, Dongguo Li^{1

2}

Affiliations

¹ School of Biomedical Engineering, Capital Medical University, Beijing, China.
² Beijing Key Laboratory of Fundamental Research on Biomechanics in Clinical, Capital Medical University, Beijing, China.
³ Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Abstract

Glioblastoma (GBM) is characterized by extensive genetic and phenotypic heterogeneity. However, it remains unexplored primarily how CpG island methylation abnormalities in promoter mediate glioblastoma typing. First, we presented a multi-omics scale map between glioblastoma sample clusters constructed based on promoter CpG island (PCGI) methylation-driven genes, using datasets including methylation profiles, expression profiles, and single-cell sequencing data from multiple highly annotated public clinical cohorts. Second, we identified differences in the tumor microenvironment between the two glioblastoma sample clusters and resolved key signaling pathways between cell clusters at the single-cell level based on comprehensive comparative analyses to investigate the reasons for survival differences between two of these clusters. Finally, we developed a diagnostic map and a prediction model for glioblastoma, and compared theoretical differences of drug sensitivity between two glioblastoma sample clusters. In summary, this study established a classification system for dissecting promoter CpG island methylation heterogeneity in glioblastoma and provides a new perspective for the diagnosis and treatment of glioblastoma.

Keywords: CpG island 3; DNA methylation 4; glioblastoma 1; intercellular communication 7; single-cell RNA sequencing 6; subtype classification 2; tumor microenviroment 5.