Spatial vascular/BTB remodeling and malignant-state plasticity in glioblastoma

Background: Glioblastoma (GBM) contains spatially heterogeneous malignant and vascular states, but blood-tumor barrier (BTB) remodeling is often described as a binary functional phenotype. We asked whether anatomically distinct GBM compartments contain separable vascular programs that coexist with malignant-state plasticity. Methods: We performed donor-aware cross-sectional analyses of 38 histopathology-annotated spatial transcriptomic sections from 6 donors and a separately analyzed endothelial single-nucleus layer from the same GBM-Space atlas. Complementary external datasets tested patient-paired regional remodeling, anatomical replication, cross-technology source localization, and malignant-state architecture. Results: THSD1-FLT4 Recognition increased from leading edge to infiltrative tumor (median adjusted effect +0.02875; 4/4 donors positive). Priming increased across this boundary (+0.14814; 3/4) but decreased from infiltrative to cellular tumor (-0.16409; 0/4), whereas Gate remodeling increased from infiltrative to cellular tumor (+0.21296; 4/4). Remodeled endothelium showed higher PLVAP detection (+0.26409; 12/12 donors) and PLVAP pseudobulk expression (+1.61784 log1pCPM; 11/12), with lower MFSD2A pseudobulk expression (-0.71448; 10/12 negative). External cohorts supported regional vascular/BTB remodeling, while GSE131928 supported broad malignant-state architecture and an exploratory within-tumor pseudotemporal continuum. Conclusions: GBM contains spatially partitioned vascular/BTB-associated programs alongside malignant-state plasticity. Recognition-Priming-Gate is a cross-sectional discovery framework, not a validated temporal cascade, and the data do not establish BTB permeability, causal tumor-vascular signaling, or therapeutic-delivery benefit.