Phosphoenolpyruvate carboxykinase 2 is a promising prognostic biomarker that correlates with peritumoral dendritic cell infiltration in glioblastoma

Background: Despite the growing interest in Phosphoenolpyruvate carboxykinase 2 (PCK2) as a potential biomarker in cancer research, studies on its clinical relevance and biological processes in glioblastoma are still unexplored. Methods: Three main glioma cohorts (TCGA, CGGA, Rembrandt) were extracted to exploit the association between PCK2 expression and clinical relevance through Kaplan-Meier survival analysis, univariate and multivariate cox regression analysis. Immunohistochemistry was used to detect PCK2 expression in glioma samples. GSEA, Pearson correlation and ROC analysis were performed to verify the specificity of PCK2 in mesenchymal GBM. Gene set variation analysis and CIBERSORT were used to explore the correlation of tumor-infiltrating immune cells according to PCK2 expression. Double immunofluorescence was performed to testify the co-expression patterns across PCK2, CD11C and PD-L1 in GBM tissues. Results: PCK2 is increasingly expressed in GBM tissues and could serve as an independent poor prognostic indicator for glioma patients. PCK2 is preferentially expressed in mesenchymal subtype and correlates with immune infiltrates and immunosuppression in glioblastoma. Furthermore, PCK2 exhibits a positive correlation with dendritic cell infiltration and is co-expressed with CD11C and PD-L1 in the peritumoral region of the GBM tissues. Additionally, the enrichment of dendritic cell signature is associated with poor prognosis in glioblastoma patients. Conclusion: Our study highlights the potential therapeutic applicability of PCK2 and PCK2 mediated dendritic cell infiltration as a mechanism for glioblastoma immunosuppression.