Yi Li, Jiang Cheng, Guo Peiquan, Zhu Wende, Jiang Xiaobing
Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
J Cancer. 2025 Jan 1;16(2):590-602. doi: 10.7150/jca.97034. eCollection 2025.
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. 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. 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. Our study highlights the potential therapeutic applicability of PCK2 and PCK2 mediated dendritic cell infiltration as a mechanism for glioblastoma immunosuppression.
尽管磷酸烯醇丙酮酸羧激酶2（PCK2）作为癌症研究中的潜在生物标志物越来越受到关注，但关于其在胶质母细胞瘤中的临床相关性和生物学过程的研究仍未得到探索。提取了三个主要的胶质瘤队列（TCGA、CGGA、伦勃朗），通过Kaplan-Meier生存分析、单因素和多因素cox回归分析来探讨PCK2表达与临床相关性之间的关联。免疫组织化学用于检测胶质瘤样本中PCK2的表达。进行基因集富集分析（GSEA）、Pearson相关性分析和ROC分析，以验证PCK2在间充质型胶质母细胞瘤中的特异性。基因集变异分析和CIBERSORT用于根据PCK2表达探索肿瘤浸润免疫细胞的相关性。进行双重免疫荧光检测，以证实胶质母细胞瘤组织中PCK2、CD11C和PD-L1的共表达模式。PCK2在胶质母细胞瘤组织中表达增加，可作为胶质瘤患者独立的不良预后指标。PCK2在间充质亚型中优先表达，与胶质母细胞瘤中的免疫浸润和免疫抑制相关。此外，PCK2与树突状细胞浸润呈正相关，并在胶质母细胞瘤组织的瘤周区域与CD11C和PD-L1共表达。此外，树突状细胞特征的富集与胶质母细胞瘤患者的不良预后相关。我们的研究强调了PCK2的潜在治疗适用性以及PCK2介导的树突状细胞浸润作为胶质母细胞瘤免疫抑制机制的可能性。
