Vascular Cell Adhesion Molecule 1 Is Associated With Immune Remodeling, Glioma Progression, and Tumor Cell Survival in U87 and U251 Cells.

The immunosuppressive microenvironment of glioma remains a major barrier to effective treatment. Vascular cell adhesion molecule 1 (VCAM1) regulates leukocyte adhesion and inflammatory signaling, but its relevance to glioma remains unresolved. Clinical and RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA), gene co-expression information from LinkOmics, and protein expression data from the Human Protein Atlas (HPA) were integrated. Kaplan-Meier analysis, Cox regression, receiver operating characteristic (ROC) analysis, and nomogram construction were used to evaluate prognostic value. Computational deconvolution was used to characterize immune cell composition, and small interfering RNA (siRNA)-mediated knockdown in U87 and U251 glioma cells was performed to evaluate VCAM1 function. VCAM1 expression was higher in glioma tissues than in normal brain tissues and increased with tumor grade. Overall survival (OS) was shorter in patients with higher VCAM1 expression, and similar findings were observed for disease-specific survival (DSS) and progression-free interval (PFI). Macrophage, regulatory T-cell, and dendritic-cell infiltration estimates were associated with VCAM1 expression, and programmed cell death 1 ligand 2 (PDCD1LG2/PD-L2) expression showed a further positive association. In cell-based assays, VCAM1 depletion reduced IL-4, IL-10, and TNF-β expression; increased IFN-γ expression; reduced MMP2, MMP9, and N-cadherin transcript levels; increased E-cadherin transcript levels; enhanced apoptosis; and reduced phosphorylation of p65, AKT, and ERK. These findings suggest that VCAM1 is associated with immune composition, inflammatory signaling, glioma cell survival, and an invasion-associated transcriptional phenotype, supporting further evaluation as a prognostic biomarker and potential therapeutic target.