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Quantifying the Brain Metastatic Tumor Micro-Environment using an Organ-On-A Chip 3D Model, Machine Learning, and Confocal Tomography
Published on: August 16, 2020
Machine learning algorithms for predicting glioma patient prognosis based on CD163+FPR3+ macrophage signature
Quanwei Zhou1, Xuejun Yan2, Youwei Guo3
1The National Key Clinical Specialty, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Abstract:
Tumor-associated macrophages (TAMs) play a vital role in glioma progression and are associated with poor outcomes in glioma patients. However, the specific roles of different subpopulations of TAMs remain poorly understood. Two distinct cell types, glioma and myeloid cells, were identified through single-cell sequencing analysis in gliomas. Within the TAMs-associated weighted gene co-expression network analysis (WGCNA) module, FPR3 emerged as a hub gene and was found to be expressed on CD163+ macrophages, while also being associated with clinical outcomes. Subsequently, a comprehensive assessment was undertaken to investigate the correlation between FPR3 expression and immune characteristics, revealing that FPR3 potentially plays a role in reshaping the glioma microenvironment. We identified a macrophage subset with the nonzero expression of CD163 and FPR3 (CD163+FPR3+). Using the expression profiles of CD163+FPR3+ macrophage-related signature, we employed ten machine learning algorithms to construct a prognostic model across six glioma cohorts. Subsequently, we employed an optimal algorithm to generate an artificial intelligence-driven prognostic signature specifically for CD163+FPR3+ macrophages. The development of this model was based on the average C-index observed in the aforementioned six cohorts. The risk score of this model consistently and effectively predicted overall survival, surpassing the accuracy of conventional clinical factors and 100 previously published signatures. Consequently, the CD163+FPR3+ macrophage-related score shows potential as a prognostic biomarker for glioma patients.
Insights
Tumor-associated macrophages (TAMs) are key in glioma. A new CD163+FPR3+ macrophage signature accurately predicts patient survival, outperforming existing methods.
Area of Science:
- Oncology
- Immunology
- Bioinformatics
Background:
- Tumor-associated macrophages (TAMs) significantly influence glioma progression and patient prognosis.
- The precise roles of distinct TAM subpopulations in glioma remain unclear.
- Single-cell sequencing identified glioma and myeloid cell types within gliomas.
Purpose of the Study:
- To investigate the role of FPR3, a hub gene in TAMs, in the glioma microenvironment.
- To identify and characterize a specific TAM subset (CD163+FPR3+) associated with clinical outcomes.
- To develop a novel prognostic model for glioma based on CD163+FPR3+ macrophage expression.
Main Methods:
- Weighted gene co-expression network analysis (WGCNA) to identify hub genes.
- Single-cell sequencing to analyze cell populations.
- Machine learning algorithms (10 models) to construct a prognostic signature.
- Validation across six independent glioma cohorts.
Main Results:
- FPR3 was identified as a hub gene within TAMs, expressed on CD163+ macrophages and linked to glioma outcomes.
- A distinct CD163+FPR3+ macrophage subset was identified.
- The developed AI-driven prognostic signature based on CD163+FPR3+ macrophages accurately predicted overall survival.
- The novel signature demonstrated superior predictive accuracy compared to clinical factors and existing biomarkers.
Conclusions:
- The CD163+FPR3+ macrophage signature holds significant potential as a prognostic biomarker for glioma.
- Targeting or understanding this specific macrophage subset could offer new therapeutic strategies for glioma.
- This study highlights the importance of macrophage heterogeneity in shaping the glioma tumor microenvironment.

