Wan Mengjiao, Zhuang Caiping, Li Wei, Yan Rongrong, Chen Wen, Cheng Jing, Yue Chengjin, Chen Lin, Quan Yingyao
Department of Anesthesiology, Maternal and Child Health Hospital of Hubei Province, Wuhan, China.
Department of Anesthesiology, Hui Zhou Central People's Hospital, Huizhou, China.
Sci Rep. 2025 Jul 22;15(1):26656. doi: 10.1038/s41598-025-12346-3.
Previous studies majorly focused on the role of driver gene variation in the occurrence, development and treatment of glioma. Here, we revealed the effect of signaling pathway abnormality by accumulated genetic mutations on patient survival and explored potential mechanism in glioma. We found that abnormalities of three signaling pathways, including autophagy-animal, focal adhesion and neuroactive ligand-receptor interaction, were associated with progression-free survival (PFS) in glioma. Based on the three pathways, we constructed and validated a biological pathway score (BPS) model to predict patient prognosis. Both PFS and overall survival (OS) were poorer in glioma patients with high BPS. In the glioma patients with high BPS, mutation frequencies of PTEN, TTN and EGFR were significantly increased. Immune checkpoints (PD-1, PD-L1 and TIM-3) were strikingly expressed in the high BPS patients with glioma, despite observed high levels of infiltrating immune cells. Differential expression genes in the high BPS patients were enriched in proliferation-related pathways. These results revealed potential reasons of poor prognosis in the high BPS patients with glioma. In addition, we found that low BPS patients with glioma might benefit from sevoflurane during surgery anesthesia. Overall, this study exhibited that the abnormalities of PFS-related signaling pathways by genetic mutations impacted survival of patients and revealed potential mechanism of poor PFS in glioma.
以往的研究主要聚焦于驱动基因变异在胶质瘤发生、发展及治疗中的作用。在此，我们揭示了累积基因突变导致的信号通路异常对患者生存的影响，并探究了胶质瘤中的潜在机制。我们发现，包括自噬-动物、粘着斑和神经活性配体-受体相互作用在内的三条信号通路异常与胶质瘤的无进展生存期（PFS）相关。基于这三条通路，我们构建并验证了一个生物通路评分（BPS）模型来预测患者预后。BPS高的胶质瘤患者的PFS和总生存期（OS）均较差。在BPS高的胶质瘤患者中，PTEN、TTN和EGFR的突变频率显著增加。尽管观察到免疫细胞浸润水平较高，但免疫检查点（PD-1、PD-L1和TIM-3）在BPS高的胶质瘤患者中显著表达。BPS高的患者中的差异表达基因在增殖相关通路中富集。这些结果揭示了BPS高的胶质瘤患者预后不良的潜在原因。此外，我们发现BPS低的胶质瘤患者在手术麻醉期间可能从七氟醚中获益。总体而言，本研究表明，基因突变导致的PFS相关信号通路异常影响患者生存，并揭示了胶质瘤中PFS不良的潜在机制。
