โก Quick Summary
This study utilized large-scale bulk and single-cell RNA sequencing combined with machine learning to uncover the heterogeneity of glioblastoma-associated neutrophils (GBMAN) and established a novel prognostic model known as the VEGFA+ neutrophil-related signature (VNRS). The VNRS model demonstrated superior accuracy compared to existing glioma risk models, highlighting its potential in guiding clinical treatment strategies for glioblastoma (GBM).
๐ Key Details
- ๐ Dataset: 127 IDH wild-type GBM samples, 498,747 cells analyzed
- ๐งฉ Features used: Single-cell RNA sequencing data
- โ๏ธ Technology: Machine learning with 117 combinations
- ๐ Performance: VNRS model outperformed existing glioma risk models
๐ Key Takeaways
- ๐ฌ Neutrophils play a critical role in the tumor microenvironment of GBM.
- ๐งฌ Four distinct neutrophil subtypes were identified within GBM samples.
- ๐ก VEGFA+ neutrophils showed reduced inflammatory responses and unique interactions with stromal cells.
- ๐ VNRS model serves as an independent prognostic factor for GBM.
- โ๏ธ Significant differences in immunotherapy responses and chemotherapy efficacy were observed between high-risk and low-risk VNRS score groups.
- ๐ The study opens new avenues for GBM immunotherapy by understanding neutrophil heterogeneity.
๐ Background
Glioblastoma (GBM) is one of the most aggressive forms of brain cancer, characterized by a complex tumor microenvironment (TME) that includes various immune cells, including neutrophils. Despite their potential significance, the role of neutrophils in GBM has been largely overlooked. This study aims to fill that gap by providing a comprehensive analysis of GBM-associated neutrophil subpopulations, which could lead to novel therapeutic strategies.
๐๏ธ Study
The research involved analyzing single-cell RNA sequencing data from 127 IDH wild-type GBM samples. The focus was on characterizing the GBMAN subgroups, exploring their developmental trajectories, cellular communication, and transcriptional networks. A total of 117 machine learning combinations were employed to develop the VNRS model, which was then compared to existing glioma risk models to assess its performance.
๐ Results
The analysis revealed a total of 5,032 neutrophils classified into four distinct subtypes. Notably, the VEGFA+GBMAN subtype exhibited a reduced inflammatory response and a propensity to interact with stromal cells. The VNRS model demonstrated higher accuracy than previously published models and was identified as an independent prognostic factor. Furthermore, significant differences in treatment responses were noted between high-risk and low-risk VNRS score groups, indicating the model’s potential utility in clinical settings.
๐ Impact and Implications
This study underscores the importance of neutrophils in the TME of GBM, providing valuable insights into their composition and characteristics. The VNRS model not only enhances our understanding of GBM biology but also serves as a promising tool for evaluating patient risk and guiding treatment strategies. The findings could pave the way for more effective immunotherapies and personalized treatment approaches in GBM management.
๐ฎ Conclusion
The research highlights the critical role of neutrophils in glioblastoma and introduces the VNRS model as a significant advancement in prognostic assessment. By leveraging machine learning and single-cell RNA sequencing, this study opens new avenues for understanding GBM and improving patient outcomes. Continued exploration of neutrophil heterogeneity may lead to innovative therapeutic strategies that enhance the efficacy of GBM treatments.
๐ฌ Your comments
What are your thoughts on the role of neutrophils in glioblastoma? Do you believe the VNRS model could change the landscape of GBM treatment? Let’s discuss! ๐ฌ Leave your thoughts in the comments below or connect with us on social media:
Large-scale bulk and single-cell RNA sequencing combined with machine learning reveals glioblastoma-associated neutrophil heterogeneity and establishes a VEGFA+ neutrophil prognostic model.
Abstract
BACKGROUND: Neutrophils play a key role in the tumor microenvironment (TME); however, their functions in glioblastoma (GBM) are overlooked and insufficiently studied. A detailed analysis of GBM-associated neutrophil (GBMAN) subpopulations may offer new insights and opportunities for GBM immunotherapy.
METHODS: We analyzed single-cell RNA sequencing (scRNA-seq) data from 127 isocitrate dehydrogenase (IDH) wild-type GBM samples to characterize the GBMAN subgroups, emphasizing developmental trajectories, cellular communication, and transcriptional networks. We implemented 117 machine learning combinations to develop a novel risk model and compared its performance to existing glioma models. Furthermore, we assessed the biological and molecular features of the GBMAN subgroups in patients.
RESULTS: From integrated large-scale scRNA-seq data (498,747 cells), we identified 5,032 neutrophils and classified them into four distinct subtypes. VEGFA+GBMAN exhibited reduced inflammatory response characteristics and a tendency to interact with stromal cells. Furthermore, these subpopulations exhibited significant differences in transcriptional regulation. We also developed a risk model termed the “VEGFA+neutrophil-related signature” (VNRS) using machine learning methods. The VNRS model showed higher accuracy than previously published risk models and was an independent prognostic factor. Additionally, we observed significant differences in immunotherapy responses, TME interactions, and chemotherapy efficacy between high-risk and low-risk VNRS score groups.
CONCLUSION: Our study highlights the critical role of neutrophils in the TME of GBM, allowing for a better understanding of the composition and characteristics of GBMAN. The developed VNRS model serves as an effective tool for evaluating the risk and guiding clinical treatment strategies for GBM.
CLINICAL TRIAL NUMBER: Not applicable.
Author: [‘Yang Y’, ‘Liu Z’, ‘Wang Z’, ‘Fu X’, ‘Li Z’, ‘Li J’, ‘Xu Z’, ‘Cen B’]
Journal: Biol Direct
Citation: Yang Y, et al. Large-scale bulk and single-cell RNA sequencing combined with machine learning reveals glioblastoma-associated neutrophil heterogeneity and establishes a VEGFA+ neutrophil prognostic model. Large-scale bulk and single-cell RNA sequencing combined with machine learning reveals glioblastoma-associated neutrophil heterogeneity and establishes a VEGFA+ neutrophil prognostic model. 2025; 20:45. doi: 10.1186/s13062-025-00640-z