Syntaxin-7 promotes EMT and tumor progression via NF-κB signaling and is associated with macrophage infiltration: pan-cancer analysis and experimental validation in hepatocellular carcinoma

Syntaxin-7 (STX7), a membrane trafficking-related gene, has been implicated in various cancers, but its specific role in hepatocellular carcinoma remains unclear. There has been no pan-cancer analysis examining the immunological function and prognostic significance of STX7 so far. We chose STX7 for an in-depth investigation to explore its expression patterns, prognostic significance, enriched pathways, and immune infiltration across various cancers. The transcriptional landscape of STX7 was examined at both single-cell and spatial levels, and a combination of in vitro and in vivo experiments was conducted to further validate its functional roles. STX7 was significantly upregulated in a wide range of cancer types and was associated with poor prognosis. Additionally, STX7 was correlated with immune cell infiltration and key immune regulators. Enrichment analysis further underscored the potential role of STX7 in immune evasion and tumor progression. Single-cell and spatial transcriptome analyses revealed its specific expression in macrophages. Functional experiments demonstrated that STX7 knockout suppressed hepatocellular carcinoma proliferation and migration, while inhibiting epithelial-mesenchymal transition (EMT) via NF-κB signaling. STX7 promotes EMT and tumor progression via NF-κB signaling, with a strong association to macrophage infiltration in cancers, including hepatocellular carcinoma, highlighting its potential as a prognostic biomarker and therapeutic target.