A novel 5-protein kinase risk signature for predicting glioma prognosis and immunotherapy responsiveness.

Glioma, among the most prevalent and heterogeneous intracranial malignancies, exhibit dismal prognoses despite advances in molecular diagnostics. Protein kinases, critical regulators of tumorigenesis, remain underexplored as systematic prognostic markers in glioma. In this study, we identified 29 differentially expressed protein kinases in TCGA (LGG and GBM) and GEO (GSE16011) databases. These dysregulated kinases were enriched in biological functions and signaling pathways related to glioma progression. Through univariate Cox, LASSO, and multivariate Cox regression, we developed a novel protein kinase prognostic risk signature comprising CAMKK2, PAK1, AK5, WEE1, and CDK4 and validated its performance to predict outcomes. We also constructed a nomogram integrating clinical characteristics and the kinase signature, which showed a high accuracy in predicting overall survival (OS) of glioma patients in TCGA, CGGA and GSE43378 cohorts. Furthermore, GSEA analysis based on risk scores revealed that various signaling pathways associated with glioma genesis and progression were enriched in the high-risk group. Immune cell infiltration analysis displayed high-risk group was characterized by a higher infiltration level of stromal and immune cells and upregulation of key immune checkpoint genes. Finally, we confirmed the protein expression of five protein kinases in glioma samples and normal samples. In conclusion, we developed a novel prognostic signature for glioma. The signature not only has potential as a prognostic biomarker but may also serve as a therapeutic target for glioma, offering new insights into glioma treatment and prognosis assessment.