GFAP-Dependent Transcriptional Dynamics and Cellular Heterogeneity in Primary, Recurrent, and Grade III Gliomas

Glioma tumors, especially glioblastoma (GBM), are among the most heterogeneous brain cancers, and this characteristic is considered the main cause of treatment resistance and disease recurrence. The aim of this study was to investigate the cellular dynamics and transcriptional pathways dependent on the GFAP gene in three clinical conditions, including grade III glioma, primary glioblastoma, and recurrent glioma.

Single-cell RNA sequencing (scRNA-seq) data from the GSE103224 collection were merged and clustered using the Seurat and Harmony software packages. Then, the Monocle3 tool was used to model cellular developmental pathways, and the Metascape database was used for functional enrichment of genes.

The results showed that malignant cells, microglia, immune cells, and glial progenitors formed distinct clusters in all conditions, and the transition of radial glial cells to cancer cells was observed in all three conditions. Differential gene expression analysis identified six genes, APOE, AQP4, CLU, GFAP, ID3, and ID4 as stable and common genes between all tumor stages, whose expression was directly related to tumor persistence and recurrence. Functional enrichment also identified steroid hormone response pathways, NGF signaling, and the VEGF pathway as common processes in glioma progression.

Overall, these results indicate that GFAP and its associated co-expression network play an important role in tumor persistence and cellular rearrangement in glioma and can be used as molecular markers and novel therapeutic targets for precise and personalized treatment of patients.