AUTHOR=Yang Guozheng , Shan Dezhi , Zhao Rongrong , Li Gang TITLE=Metabolism-Associated DNA Methylation Signature Stratifies Lower-Grade Glioma Patients and Predicts Response to Immunotherapy JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=10 YEAR=2022 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.902298 DOI=10.3389/fcell.2022.902298 ISSN=2296-634X 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.