Malignant progression of MES-like cells mediated by COL22A1 in the spatial heterogeneity of glioblastoma

Abstract Glioblastoma (GBM), a highly aggressive malignant brain tumor, leads to poor clinical outcomes and low long-term survival rates. Using bioinformatics approaches, we analyzed single-cell RNA sequencing (scRNA-seq) data (GSE273274) from glioma patient samples in this study. It was found that mesenchymal-like (MES-like) cells in the GBM center (GC) significantly facilitated GBM’s aggressive spread and microenvironmental reprogramming. Further analysis on MES-like cells suggested that these cells may participate in the progression from glial differentiation to invasive metastasis. Differential expression analysis, univariate Cox regression, and LASSO regression identified COL22A1 as a key gene. COL22A1 was highly expressed in GC compared to GBM surrounding tissue (GS) and exhibited potential connection to aberrant phosphatidylinositol 3-kinase (PI3K) signaling activation, indicating that COL22A1 may act as a potential regulator of GBM, promoting malignant processes such as proliferation, apoptosis resistance, migration, and invasion. In vitro experiments showed that COL22A1 overexpression (COL22A1-OE) U-87 cells exhibited enhanced proliferation, viability, migration, and invasion. Moreover, immunoblotting of BCL-2 and BAX revealed that COL22A1-OE increased resistance to apoptosis in U-87 cells. However, all these effects were reversed upon silencing of COL22A1, which suggests COL22A1 could be a promising new target for GBM therapy.