Abstract
Glioma is a prevalent malignant tumour characterized by hypoxia as a pivotal factor in its progression. This study aims to investigate the impact of the most severely hypoxic cell subpopulation in glioma. Our findings reveal that the THBD(+) macrophage subpopulation is closely associated with hypoxia in glioma, exhibiting significantly higher infiltration in tumours compared to non-tumour tissues. Moreover, a high proportion of THBD(+) cells correlates with poor prognosis in glioblastoma (GBM) patients. Notably, THBD(+) macrophages exhibit hypoxic characteristics and epithelial-mesenchymal transition features. Silencing THBD expression leads to a notable reduction in the proliferation and metastasis of glioma cells. Furthermore, we developed a THBD(+) macrophage-related risk signature (THBDMRS) through machine learning techniques. THBDMRS emerges as an independent prognostic factor for GBM patients with a substantial prognostic impact. By comparing THBDMRS with 119 established prognostic features, we demonstrate the superior prognostic performance of THBDMRS. Additionally, THBDMRS is associated with glioma metastasis and extracellular matrix remodelling. In conclusion, hypoxia-related THBD(+) macrophages play a pivotal role in glioma pathogenesis, and THBDMRS emerges as a potent and promising prognostic tool for GBM, contributing to enhanced patient survival outcomes.