Glycosylation modification patterns reveal distinct tumor metabolism and immune microenvironment landscape in lower-grade gliomas

Abstract

Glycosylation alterations, a key driver throughout tumorigenesis and tumor progression, could regulate the microenvironment and immune response as well as lead to harmful metabolism and cell signaling. In this study, we first comprehensively evaluated the glycosylation modification patterns of LGGs based on glycosyltransferase family genes and systematically integrated these modification patterns with tumor metabolism and immune microenvironment characteristics. Glycosylation score was also developed to quantify glycosylation modification patterns of individuals. As a result, two glycosylation modification patterns were identified, with distinct prognosis, metabolism, and immune microenvironment features. The glycosylation subtype A and cluster A were characterized by higher carbohydrates and amino acid metabolism activity, higher levels of infiltrating cells, and poor prognosis, whereas an opposite modification pattern was observed in glycosylation subtype B and cluster B. In addition, a high glycosylation score is closer to a microenvironment characterized by chronic inflammation, immunosuppression, and tumor promotion. Following analysis and validation, the glycosylation score was a reliable and independent prognostic index. More importantly, the glycosylation score influenced the response to immunotherapy, chemotherapy, or targeted therapy, which provided a novel insight into promoting personalized therapy in the future and may contribute to developing novel therapeutic drugs or exploring promising drug combination therapy strategies.