Tumor Sialylation-Associated Co-expression of ST6GAL1 and SIGLEC7 Suggests a Glyco-Immune Regulatory Signature in Low-Grade Glioma

Abstract

Background: Tumor cells can evade immune destruction through several mechanisms; however, the role of altered cell-surface glycosylation in regulating immune responses in glioma remains incompletely understood. Sialic acids are terminal glycan residues that may inhibit cytotoxic immune responses by interacting with inhibitory receptors on immune cells. Objectives: This study investigated whether exposure to sialic acid affects the expression of the sialyltransferase ST6GAL1 and its potential association with the inhibitory receptor SIGLEC7 in glioma. Methods: Human astrocytoma 1321N1 cells were treated with exogenous sialic acid, and ST6GAL1 and SIGLEC7 expression was assessed using quantitative PCR and Western blotting. To evaluate clinical relevance, transcriptomic datasets from low-grade glioma (LGG) in The Cancer Genome Atlas (TCGA) were analyzed to examine gene expression patterns, co-expression relationships, and pathway enrichment. Results: Treatment with exogenous sialic acid increased ST6GAL1 and SIGLEC7 expression compared with untreated controls. Analysis of patient data showed elevated expression of both genes in LGG tumor samples and a significant positive correlation between their expression levels. Heatmap analysis further indicated that tumors with higher ST6GAL1 and SIGLEC7 expression also showed increased expression of cytotoxic immune markers, including CD8A, PRF1, NCAM1, and GZMB. Pathway enrichment analysis showed significant enrichment of biological processes related to glycosylation and sialylation. Conclusions: The in vitro findings indicate that sialic acid modulates ST6GAL1 and SIGLEC7 expression in astrocytoma cells. Transcriptomic associations observed in patient data suggest a potential relationship between ST6GAL1 and SIGLEC7 expression in LGG tumors, along with increased expression of selected cytotoxic immune-related transcripts that may contribute to immune regulatory processes. Collectively, these hypothesis-generating observations raise the possibility of a glyco-immune regulatory mechanism in glioma and highlight tumor sialylation as a potential factor contributing to immune escape. Further mechanistic and functional studies are required to determine whether a direct biological relationship exists between ST6GAL1 and SIGLEC7 in glioma.