Single-cell analysis reveals KLF10-high macrophages induced by glioblastoma cells are associated with tumor...

Glioblastoma (GBM) is the most common and aggressive primary malignant tumor of the adult central nervous system, with nearly 90% of cases recurring within two years despite standard surgery, radiotherapy, and chemotherapy. Tumor-associated macrophages (TAMs) play critical roles in GBM recurrence, but their characteristics in recurrent GBM remain insufficiently defined. Krüppel-like factor 10 (KLF10) regulates metabolism, mitochondrial function, proliferation, and apoptosis; however, its role in GBM-associated TAMs remains unclear.

Single-cell RNA-sequencing data from 16 GBM samples were analyzed to identify recurrence-associated TAMs. Functional features were assessed using GO, KEGG, and CellChat analyses. Marker genes were used to construct a prognostic signature through LASSO and Cox regression. The association between KLF10 and clinicopathological features was evaluated using TCGA data. A GBM cell-macrophage co-culture system was established to examine KLF10 induction, and KLF10-overexpressing macrophages were used to assess effects on GBM-cell proliferation, migration, and invasion.

A five-gene prognostic signature comprising KLF10, ZFAND2A, SMAD7, GPR84, and ARHGAP12 was identified. KLF10 expression was associated with WHO grade, IDH mutation, MGMT promoter methylation, 1p/19q co-deletion, molecular subtype, and overall survival, with high KLF10 predicting poor prognosis. Functional enrichment analyses suggested that KLF10-associated genes were linked to ECM-receptor interaction, cell-cycle-related pathways, and cytokine signaling. In vitro, co-culture with GBM cells upregulated KLF10 expression in THP-1-derived macrophages, and KLF10-overexpressing macrophages were associated with increased GBM-cell proliferation, migration, and invasion.

KLF10-high macrophages were associated with GBM progression and may serve as a candidate prognostic marker requiring further validation.