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

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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