Ye Hong-Xing, Zhang Chao, He Long-Yuan, Lan Ping, Wang Feng, Zhan Ren-Ya, Zheng Xiu-Jue
Department of Neurosurgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Eur J Med Res. 2025 Jul 2;30(1):545. doi: 10.1186/s40001-025-02808-9.
Gliomas are aggressive brain tumors with high mortality and recurrence rates. Pleiotrophin (PTN), a cytokine that interacts with heparin, is upregulated in several cancers, including breast and lung cancer. PTN is implicated in cancer progression, recurrence, epithelial-mesenchymal transition (EMT), and metastasis. However, the role of PTN in glioma progression remains poorly understood. This study aimed to investigate the expression profile of PTN in glioma and its potential prognostic significance.
The expression levels of PTN in glioma samples were analyzed using data from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). Gene Ontology (GO) term analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to identify PTN-associated pathways. In vitro experiments were performed to assess the impact of PTN suppression on glioma cell growth, cell cycle progression, migration, and invasion. In addition, gene set enrichment analysis (GSEA) and Western blot were employed to investigate the link between PTN and NF-κB signaling pathways.
PTN expression was significantly higher in glioma samples, and elevated PTN levels were associated with decreased overall survival. GO term and KEGG analysis showed that PTN is primarily linked to pathways related to cell mitosis, including the cell cycle and DNA replication. In vitro experiments demonstrated that the suppression of PTN inhibited glioma cell growth, arrested the cell cycle in the G0/G1 phase, and impaired the migratory and invasive capabilities of glioma cells. GSEA revealed a significant correlation between PTN and the NF-κB pathway. Further investigation showed that PTN suppression inhibited NF-κB activation and IκB phosphorylation, thereby preventing Slug-induced EMT in glioma cells.
PTN plays a crucial role in glioma progression by regulating cell proliferation, migration, invasion, and EMT through the NF-κB pathway. PTN may serve as an important prognostic biomarker and therapeutic target in glioma treatment.
胶质瘤是具有高死亡率和复发率的侵袭性脑肿瘤。多效生长因子（PTN）是一种可与肝素相互作用的细胞因子，在包括乳腺癌和肺癌在内的多种癌症中表达上调。PTN与癌症进展、复发、上皮-间质转化（EMT）及转移有关。然而，PTN在胶质瘤进展中的作用仍知之甚少。本研究旨在调查PTN在胶质瘤中的表达谱及其潜在的预后意义。
利用来自癌症基因组图谱（TCGA）和中国胶质瘤基因组图谱（CGGA）的数据，分析胶质瘤样本中PTN的表达水平。进行基因本体（GO）术语分析和京都基因与基因组百科全书（KEGG）通路分析，以识别与PTN相关的通路。开展体外实验，评估抑制PTN对胶质瘤细胞生长、细胞周期进程、迁移和侵袭的影响。此外，采用基因集富集分析（GSEA）和蛋白质免疫印迹法研究PTN与核因子κB（NF-κB）信号通路之间的联系。
PTN在胶质瘤样本中的表达显著更高，且PTN水平升高与总生存期降低相关。GO术语和KEGG分析表明，PTN主要与细胞有丝分裂相关的通路有关，包括细胞周期和DNA复制。体外实验表明，抑制PTN可抑制胶质瘤细胞生长，使细胞周期停滞在G0/G1期，并损害胶质瘤细胞的迁移和侵袭能力。GSEA显示PTN与NF-κB通路之间存在显著相关性。进一步研究表明，抑制PTN可抑制NF-κB激活和IκB磷酸化，从而阻止胶质瘤细胞中Slug诱导的EMT。
PTN通过NF-κB通路调节细胞增殖、迁移、侵袭和EMT在胶质瘤进展中起关键作用。PTN可能是胶质瘤治疗中的重要预后生物标志物和治疗靶点。
