E-ISSN: 1019-5157
ISSN: 2651-5024
Research
Analysis of Genomes and Transcriptomes of glioma Identifies Mutations and Gene Expression Changes in the Transforming Growth Factor beta Pathway
Luo Xiaodong✉ ,
Zhang Bo ,
Yang Qiang ,
Yang Hu ,
Dong Jinqian ,
Dong Zhiqiang ,
Li Qiang
Li Qiang
Neurosurgery, Lanzhou University Second Hospital
Article in Press
Corresponding Author:
Luo Xiaodong (ldyy_luoxd@lzu.edu.cn)
Abstract
Aim
Glioblastoma (GBM) is the most aggressive malignant brain tumor in adults, with poor prognosis despite current standard treatments. While immune checkpoint inhibitors (ICIs) such as PD-1 blockade have shown promise in several cancers, their efficacy in GBM remains limited, with a response rate of approximately 20%. Transforming growth factor β (TGF-β) is known to contribute to glioma progression and immune suppression, yet its precise role in GBM remains unclear.
Material and Methods
We conducted hierarchical clustering based on TGF-β pathway gene expression in 922 GBM samples, stratifying them into TGF-β-activated and TGF-β-inactivated subgroups. We analyzed differences in survival outcomes, immune cell infiltration, signaling pathway enrichment, mutation profiles, and predicted drug sensitivities between the two subgroups.
Results
The TGF-β-inactivated subgroup exhibited significantly better survival than the activated subgroup. The activated subgroup was enriched in immunosuppressive cell typesincluding M0/M2 macrophages, mast cells, neutrophils, and dendritic cellsand showed high activity in the JAK-STAT, TP53, and toll-like receptor pathways. In contrast, the inactivated subgroup had elevated CD8+ T cells and a higher TP53 mutation rate, suggesting a more immunologically active environment. Drug response analysis revealed that Roscovitine, Dasatinib, Paclitaxel, PD-0325901, Bryostatin-1, BMS-536924, AZD7762, and A-770041 may be more effective in this subgroup.
Conclusion
The activation state of the TGF-β signaling pathway is closely associated with prognosis, immune landscape, and drug sensitivity in glioblastoma. These findings provide insights into the immunological role of TGF-β in GBM and may support the development of personalized treatment strategies targeting TGF-β-associated pathways.
Glioblastoma (GBM) is the most aggressive malignant brain tumor in adults, with poor prognosis despite current standard treatments. While immune checkpoint inhibitors (ICIs) such as PD-1 blockade have shown promise in several cancers, their efficacy in GBM remains limited, with a response rate of approximately 20%. Transforming growth factor β (TGF-β) is known to contribute to glioma progression and immune suppression, yet its precise role in GBM remains unclear.
Material and Methods
We conducted hierarchical clustering based on TGF-β pathway gene expression in 922 GBM samples, stratifying them into TGF-β-activated and TGF-β-inactivated subgroups. We analyzed differences in survival outcomes, immune cell infiltration, signaling pathway enrichment, mutation profiles, and predicted drug sensitivities between the two subgroups.
Results
The TGF-β-inactivated subgroup exhibited significantly better survival than the activated subgroup. The activated subgroup was enriched in immunosuppressive cell typesincluding M0/M2 macrophages, mast cells, neutrophils, and dendritic cellsand showed high activity in the JAK-STAT, TP53, and toll-like receptor pathways. In contrast, the inactivated subgroup had elevated CD8+ T cells and a higher TP53 mutation rate, suggesting a more immunologically active environment. Drug response analysis revealed that Roscovitine, Dasatinib, Paclitaxel, PD-0325901, Bryostatin-1, BMS-536924, AZD7762, and A-770041 may be more effective in this subgroup.
Conclusion
The activation state of the TGF-β signaling pathway is closely associated with prognosis, immune landscape, and drug sensitivity in glioblastoma. These findings provide insights into the immunological role of TGF-β in GBM and may support the development of personalized treatment strategies targeting TGF-β-associated pathways.
Keywords
Transforming Growth Factor beta
prognosis
mutation
Glioblastoma