STC1 is associated with tumor progression and suppressive niches in laryngeal squamous cell carcinoma.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) exhibits high recurrence and therapy resistance. We aimed to investigate the undefined role of Stanniocalcin-1 (STC1) in LSCC pathogenesis. METHODS: The single-cell RNA sequencing (RNA-seq) data and the clinical information of LSCC patients were acquired from the public database. Prognostic differences and diagnostic efficiency of STC1 were assessed. The gene correlation was investigated by Spearman method. Enrichment analysis was performed using clusterProfiler, and immune infiltration was assessed with CIBERSORT. Finally, we analyzed the distribution of specific STC1 expression in cell types using single-cell RNA sequencing (scRNA-seq) analysis, and cell communication for ligand-receptor interactions between STC1+ cells and T cell subsets. RESULTS: The upregulated STC1 was linked to tumor metastasis and disease stage in LSCC. It correlated with genes involved in extracellular matrix (ECM) remodeling, epithelial-mesenchymal transition (EMT), phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt), and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) resistance. High STC1 expression was linked to an immunosuppressive microenvironment, with increased M0 macrophages and reduced CD8+ T cells, and was positively correlated with the immune checkpoints [programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), T cell immunoglobulin and ITIM domain (TIGIT), T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3)]. Single-cell analysis localized STC1 to epithelial cells, with STC1+ epithelial cells showing enriched endoplasmic reticulum (ER) stress, inflammatory signaling, and EMT during carcinogenesis. Cell-cell communication analysis revealed that STC1+ epithelial cells engage T cell subsets through more ligand-receptor pairs in the transforming growth factor-beta (TGF-β) and B- and T-lymphocyte attenuator (BTLA) pathways compared to STC1- epithelial cells. CONCLUSIONS: These findings indicate STC1 is strongly correlated with signatures of immune evasion and malignant progression in LSCC, suggesting that targeting STC1 may reprogram the immunosuppressive microenvironment and improve therapeutic outcomes.