HOXD8 drives Glioma progression through epithelial-mesenchymal transition regulation: Implications for prognosis and targeted therapy

Glioma is one of the most common primary malignant tumors of the central nervous system. Here, we defined Homeobox D8 (HOXD8) as a novel biomarker for glioma utilizing RNA-sequencing and bioinformatics approaches. HOXD8 expression was significantly upregulated in glioma cell lines (U251 and U373) and clinical specimens compared to normal controls. Functional studies demonstrated that HOXD8 knockdown markedly inhibited glioma cell proliferation, migration, and invasion in vitro. Additionally, pan-cancer analysis revealed significant associations between HOXD8 expression and key tumor characteristics, including immune cell infiltratio, tumor mutational burde, and microsatellite instability. Meanwhile, transcriptomic profiling and pathway analysis identified HOXD8's involvement in epithelial-mesenchymal transition (EMT) regulation, with Western blot validation showing significant modulation of EMT markers following HOXD8 knockdown. Collectively, our results suggests that HOXD8 may serve as a satisfactory prognostic biomarker that promotes glioma cell proliferation, migration and invasion, potentially through regulation of EMT processes.