Wang Delin, Liu Cuimei, Sun Bohao, Zhang Xiaodong, Zhou Yejun, Hu Zhonglin, Cao Duanzheng, Zhang Jing, Xu Jinfang
Department of Neurosurgery, Jiande First People's Hospital, Hangzhou, Zhejiang, China.
Department of Neurology, Jiande First People's Hospital, Hangzhou, Zhejiang, China.
PeerJ. 2025 Jul 10;13:e19675. doi: 10.7717/peerj.19675. eCollection 2025.
Glioma, a highly aggressive brain tumor, presents significant challenges in prognosis and treatment. This study investigates the role of PTX3 expression in glioma and its correlation with patient outcomes, addressing a gap in current research regarding its molecular mechanisms.
RNA sequencing data and clinical information for glioma patients were obtained from The Cancer Genome Atlas (TCGA). A multigene prognostic signature based on IL-18 signaling-related genes (ISRGs) was constructed using the least absolute shrinkage and selection operator (LASSO) Cox regression method. The functional roles of PTX3 were analyzed through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). Single-sample GSEA (ssGSEA) was used to assess the association between PTX3 expression and immune cell infiltration. The relationship between PTX3 expression and clinicopathological features was also examined. Prognostic relevance was evaluated using univariate and multivariate Cox regression models, and Kaplan-Meier survival analysis was performed. PTX3 protein expression was validated immunohistochemistry in 56 glioma specimens.
The LASSO Cox regression model identified a nine-gene prognostic signature, including BMP2, NCF1, HSPB1, PIGT, PTX3, CCNA2, CCNB2, CCN4, and DES. Functional enrichment analysis revealed that PTX3-associated differentially expressed genes were significantly enriched in pathways such as cytokine-cytokine receptor interaction and PI3K-Akt signaling, which are critical for immune response and cell proliferation in glioma. PTX3 expression showed a strong correlation with immune cell infiltration, particularly macrophages, neutrophils, T cells, and natural killer cells, suggesting a role in modulating the tumor microenvironment. Pan-cancer analysis indicated that PTX3 is markedly upregulated in various cancers, especially gliomas, highlighting its potential as a biomarker. PTX3 expression was also associated with clinical features such as WHO grade, IDH mutation status, and 1p/19q co-deletion, with higher PTX3 levels linked to poorer survival outcomes. Immunohistochemistry confirmed elevated PTX3 protein expression in both lower-grade glioma and glioblastoma multiforme.
These findings highlight the critical role of PTX3 in glioma and suggest its potential as both a prognostic biomarker and therapeutic target. This study provides a foundation for future research into targeted therapies involving PTX3.
胶质瘤是一种高度侵袭性的脑肿瘤，在预后和治疗方面存在重大挑战。本研究调查了PTX3表达在胶质瘤中的作用及其与患者预后的相关性，填补了当前关于其分子机制研究的空白。
从癌症基因组图谱（TCGA）获取胶质瘤患者的RNA测序数据和临床信息。使用最小绝对收缩和选择算子（LASSO）Cox回归方法构建基于白细胞介素-18信号相关基因（ISRGs）的多基因预后特征。通过基因本体论（GO）、京都基因与基因组百科全书（KEGG）和基因集富集分析（GSEA）分析PTX3的功能作用。使用单样本GSEA（ssGSEA）评估PTX3表达与免疫细胞浸润之间的关联。还检查了PTX3表达与临床病理特征之间的关系。使用单变量和多变量Cox回归模型评估预后相关性，并进行Kaplan-Meier生存分析。在56例胶质瘤标本中通过免疫组织化学验证PTX3蛋白表达。
LASSO Cox回归模型确定了一个九基因预后特征，包括BMP2、NCF1、HSPB1、PIGT、PTX3、CCNA2、CCNB2、CCN4和DES。功能富集分析表明，与PTX3相关的差异表达基因在细胞因子-细胞因子受体相互作用和PI3K-Akt信号传导等通路中显著富集，这些通路对胶质瘤中的免疫反应和细胞增殖至关重要。PTX3表达与免疫细胞浸润密切相关，尤其是巨噬细胞、中性粒细胞、T细胞和自然杀伤细胞，表明其在调节肿瘤微环境中发挥作用。泛癌分析表明，PTX3在各种癌症中明显上调，尤其是胶质瘤，突出了其作为生物标志物的潜力。PTX3表达还与世界卫生组织（WHO）分级、异柠檬酸脱氢酶（IDH）突变状态和1p/19q共缺失等临床特征相关，PTX3水平越高，生存结果越差。免疫组织化学证实低级别胶质瘤和多形性胶质母细胞瘤中PTX3蛋白表达均升高。
这些发现突出了PTX3在胶质瘤中的关键作用，并表明其作为预后生物标志物和治疗靶点的潜力。本研究为未来涉及PTX3的靶向治疗研究奠定了基础。
