Metabolism-Associated DNA Methylation Signature Stratifies Lower-Grade Glioma Patients and Predicts Response to Immunotherapy

Abstract

Metabolism and DNA methylation (DNAm) are closely linked. The value of the metabolism-DNAm interplay in stratifying glioma patients has not been explored. In the present study, we aimed to stratify lower-grade glioma (LGG) patients based on the DNAm associated with metabolic reprogramming. Four data sets of LGGs from three databases (TCGA/CGGA/GEO) were used in this study. By screening the Kendall’s correlation of DNAm with 87 metabolic processes from KEGG, we identified 391 CpGs with a strong correlation with metabolism. Based on these metabolism-associated CpGs, we performed consensus clustering and identified three distinct subgroups of LGGs. These three subgroups were characterized by distinct molecular features and clinical outcomes. We also constructed a subgroup-related, quantifiable CpG signature with strong prognostic power to stratify LGGs. It also serves as a potential biomarker to predict the response to immunotherapy. Overall, our findings provide new perspectives for the stratification of LGGs and for understanding the mechanisms driving malignancy.

Biomarkers and experimental models for cancer immunology investigation

“…47 By calculating the scores of a series of key gene phenotypes within the CIMP subtype, predictions can be made regarding the therapeutic prognosis of patients. 47,148,149 Besides, ICB response prediction models utilizing DNA methylation profiles have emerged for several cancer types including melanoma, 150 esophagus carcinoma, 48 NSCLC, 151 glioma, 152 and bladder cancer. 153 However, despite the potential of DNA methylation being a reliable biomarker in various cancers, fundamental exploration is still needed.…”