Integrative Analysis of DNA Methylation and Transcriptome Identifies a Predictive Epigenetic Signature Associated With Immune Infiltration in Gliomas.

Jianlei Zhang,Ning Xu,Dongfeng Zhai,Guopei Zheng,Liyun Luo,Mingqiang Yang,Danqing Huang,Jiang Yin,Ge Wang,Qiong Zhang,Ying Song

doi:10.3389/fcell.2021.670854

Jianlei Zhang, Ning Xu + Show 9 more

Open Access

https://doi.org/10.3389/fcell.2021.670854

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Abstract

Glioma is the most common primary brain tumor with poor prognosis and high mortality. The purpose of this study was to use the epigenetic signature to predict prognosis and evaluate the degree of immune infiltration in gliomas. We integrated gene expression profiles and DNA methylation data of lower-grade glioma and glioblastoma to explore epigenetic differences and associated differences in biological function. Cox regression and lasso analysis were used to develop an epigenetic signature based on eight DNA methylation sites to predict prognosis of glioma patients. Kaplan–Meier analysis showed that the overall survival time of high- and low-risk groups was significantly separated, and ROC analysis verified that the model had great predictive ability. In addition, we constructed a nomogram based on age, sex, 1p/19q status, glioma type, and risk score. The epigenetic signature was obviously associated with tumor purity, immune checkpoints, and tumor-immune infiltrating cells (CD8+ T cells, gamma delta T cells, M0 macrophages, M1 macrophages, M2 macrophages, activated NK cells, monocytes, and activated mast cells) and thus, it may find application as a guide for the evaluation of immune infiltration or in treatment decisions in immunotherapy.

Highlights

Gliomas are the most common primary tumors of the central nervous system, accounting for 60% of craniocerebral tumors (Ostrom et al, 2019)
Because DNA methylation in promoter regions significantly affects gene expression, we analyzed the TSS200 and TSS1500 sites located in transcription start sites, and as a result, 145,907 methylation sites were filtered for subsequent study
The immunostaining score of interferon induced protein 44 (IFI44) was positively correlated with CD68 and CD206 expression (Figure 7F). These results suggested that spondin 2 (SPON2) may be involved in the recruitment of non-M2 macrophages, while IFI44 may participate in the recruitment of M2 macrophages

Summary

Introduction

Gliomas are the most common primary tumors of the central nervous system, accounting for 60% of craniocerebral tumors (Ostrom et al, 2019). According to the malignant features, the World Health Organization (WHO) divides gliomas into four grades. With the continuous discovery of new molecular markers, the accurate classification of gliomas has been promoted. The WHO recommends that molecular markers such as co-deletion of chromosome arms 1p and 19q (1p/19q co-deletion) and isocitrate dehydrogenase (IDH) mutation status be included in the histopathological classification of gliomas (Louis et al, 2016). Surgery combined with chemotherapy or radiotherapy is a common treatment strategy for gliomas, but the prognosis varies greatly (van den Bent et al, 2013; van den Bent, 2014; Buckner et al, 2016). Multi-omics Approach in Glioma Prognosis glioblastoma (GBM), or grade 4 glioma, is the most common and fatal malignant brain tumor, with a short median survival of only 12 to 15 months (Hanif et al, 2017). The development of effective biomarkers for risk assessment may help to guide the choice of future targeted treatment strategies

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