COL8A1 as a pro-inflammatory mediator bridges immune evasion and therapy resistance in glioma

Glioma remains the most aggressive and therapy-resistant brain tumor, with a highly immunosuppressive tumor microenvironment. The role of inflammatory signaling in glioma progression and treatment response is poorly understood.

We performed single-cell RNA sequencing (scRNA-seq) analysis on 93,027 cells from 18 samples. Inflammation-related genes were identified using hdWGCNA and AUCell scoring. Multiple bulk RNA-seq and microarray datasets were integrated for validation. Machine learning algorithms, including CoxBoost, LASSO, and Random Survival Forest, were used to identify prognostic genes. Immune infiltration, immunotherapy response, and mutational landscape were analyzed using established computational tools.

COL8A1 was found to be a significant prognostic gene within a highly linked gene module connected to inflammation. Astrocytes, OPCs, and cancerous cells all had high levels of COL8A1 expression. In several cohorts, low survival was linked to high COL8A1 expression. The suppression of tumor migration and proliferation by COL8A1 knockdown was validated by functional tests. Multiple immunotherapy determinants, inhibitory immunological checkpoints, and immune cell infiltration all showed high correlations with COL8A1 expression. Additionally, it accurately forecasted the immune checkpoint blockade response. Through mutational profiling, we identified distinct somatic mutation patterns distinguishing COL8A1-high from COL8A1-low cancers.

By connecting tumor-intrinsic inflammation to immunological surveillance and treatment resistance, our study identified COL8A1 as a crucial inflammatory hub in glioma. In order to improve the results of immunotherapy for glioma, COL8A1 may be a useful therapeutic target and prognostic biomarker.