Diagnostic and prognostic significance of tetraspanin 6 and its role in facilitating glioma progression

Abstract

Abstract Background Several tetraspanin (TSPAN) proteins have been implicated in tumorigenesis and disease progression. However, the precise function of tetraspanin 6 (TSPAN6) in glioma remains unclear. Methods Integrated raw data from the Tumor Genome Atlas (TCGA) and Gene Expression Profiling (GEO) databases were processed using R4.2.1. Bioinformatic methods were used to analyze the gene expression levels of TSPAN6 in both glioma and normal brain tissues, correlating them with clinical characteristics. Additionally, the predictive value of TSPAN6 in relation to the immune checkpoint blockade (ICB) therapy response was assessed. In vitro experiments were conducted to investigate the effects of TSPAN6 knockdown on glioma cell proliferation, migration, cell cycle regulation, and macrophage recruitment. Results TSPAN6 expression was significantly upregulated in glioma tissues compared to normal tissues. Elevated TSPAN6 expression is strongly correlated with unfavorable clinical characteristics in gliomas. Bioinformatic analyses revealed a significant correlation between elevated TSPAN6 expression and reduced overall survival. Additionally, TSPAN6 was co-expressed with several immune checkpoint genes and revealed a prognostic value in the context of ICB therapy. Functional enrichment analysis revealed the involvement of TSPAN6 in cell-cycle regulation. Furthermore, TSPAN6 expression positively correlated with macrophage and neutrophil infiltration. In vitro experiments confirmed that the downregulation of TSPAN6 inhibited U251 cell proliferation, disrupted the cell cycle, diminished migratory capabilities, and reduced the recruitment of macrophages. Conclusion Our findings emphasize its potential as both a diagnostic and therapeutic target as well as a predictor of immune therapy response in gliomas.

Keywords

• Glioma
• TSPAN6
• Prognosis
• Immune infiltration
• Immune checkpoint