Identification of an age-related monocyte-derived macrophages characteristic genes-based signature for high-grade diffuse glioma

Monocyte-derived macrophages (MDMs) have been associated with increased infiltration proportion and shorter overall survival (OS) in diffuse gliomas (DGs), particularly contributing to poor prognosis in elderly patients. However, the criteria for predicting the suitability and efficacy of MDM-targeted therapy in cancer treatment remain unclear. This study utilized TCGA and CGGA high-grade diffuse glioma cohorts (IDH-wildtype glioblastoma or IDH-mutant astrocytoma, CNS WHO grade 4) with complete mRNA expression profiles and clinical information. The MDM intersect gene set was obtained through differential gene analysis and single cell RNA-sequencing analysis, followed by the application of least absolute shrinkage and selection operator (LASSO) algorithm to identify core genes for risk score (RS) modeling. Using the TCGA dataset as a training set and CGGA dataset as a validation set, we verified that RS, including G0S2, PLAUR, and SPAG4 gene expressions, is a reliable indicator of poor prognosis in high-grade DGs patients. Our findings demonstrate that RS can serve as an infiltration index for MDMs enabling accurate prediction of high-grade DGs patient prognosis. Furthermore, we found that in glioblastoma (GBM), a more malignant subtype of diffuse glioma, monitoring this index and targeting MDMs is crucial for improving overall survival, especially in older female patients.