Journal Article Epublish
PubMed: 40696074 DOI: 10.1038/s41598-025-12346-3
Mutational accumulation drives pathway dysregulation to predict glioma patient survival.
Sci Rep 15(1):26656
Authors: Mengjiao Wan, Caiping Zhuang, Wei Li, Rongrong Yan, Wen Chen, Jing Cheng, Chengjin Yue, Lin Chen, Yingyao Quan
Affiliations
- Department of Anesthesiology, Maternal and Child Health Hospital of Hubei Province, Wuhan, China.
- Department of Anesthesiology, Hui Zhou Central People's Hospital, Huizhou, China.
- The Second Department of General Surgery, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, China.
- Department of Anesthesiology, Maternal and Child Health Hospital of Hubei Province, Wuhan, China.
- Department of Anesthesiology, Maternal and Child Health Hospital of Hubei Province, Wuhan, China.
Abstract
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.
MeSH
Genes, Glioma, Mutation, Prognosis