Phosphoenolpyruvate carboxykinase 2 as a prognostic biomarker: expression and clinical significance in Group 3 and Group 4 medulloblastoma.

[PURPOSE] Despite Phosphoenolpyruvate carboxykinase 2 (PCK2) has attracted growing attention as a potential biomarker in cancer research, its role in medulloblastoma (MB) remains unclear. This research aims to evaluate PCK2 as a novel biomarker for groups 3 and 4 MB and to investigate its associations with prognosis and the tumor immune microenvironment.

[METHODS] Five cohorts were extracted to identify characteristic genes associated with MB molecular subtypes through gene differential expression analysis and machine learning techniques. Kaplan-Meier survival analysis, alongside univariate and multivariate COX regression analyses, was employed to investigate the relationship between expression and clinical significance. Immunohistochemistry was used to detect expression in MB samples. ROC analysis was performed to verify the specificity of . MCP-counter, CIBERSORT, and ssGSEA were used to explore the correlation of tumor-infiltrating immune cells according to expression. Immunofluorescence was performed to testify the co-expression patterns across PCK2, CD206 and PD-L1 in MB tissues.

[RESULTS] is increasingly expressed in Group 3 MB and could serve as an independent poor prognostic indicator for MB patients. correlates with immune infiltrates and immunosuppression. Furthermore, exhibits a positive correlation with M2-type macrophage infiltration and is co-expressed with CD206 and PD-L1 in MB tissues.

[CONCLUSION] Our study demonstrates that PCK2 may serve as a reliable biomarker for differentiating Group 3 from Group 4 MB and could potentially play a role in immunotherapy-related mechanisms.

[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1007/s11060-025-05416-z.