Systematic Pan-Cancer Analysis of the Oncogenic and Immunological Function of Stanniocalcin-1 (STC1).

Abstract

Background: Stanniocalcin 1 (STC1) has been implicated in cancer pathogenesis, yet its pan-cancer implications and mechanistic roles in tumor progression and immune modulation remain incompletely characterized. The clinical relevance of STC1 in predicting prognosis and its interaction with tumor immune microenvironment components require systematic investigation.

Objective: This study aims to establish the pan-cancer prognostic significance of STC1 and elucidate its associations with immunological characteristics, including immune checkpoint proteins, tumor mutational burden (TMB), microsatellite instability (MSI), and immune cell infiltration. We specifically focus on validating its role in gastric adenocarcinoma (STAD) pathogenesis.

Methods: Multi-omics analysis was performed using TCGA pan-cancer datasets and bioinformatics tools (UALCAN, cBioPortal, HPA, GTA). Experimental validation included multiplex fluorescence staining of STAD tissue microarrays (n=30) and Western blot analysis of STAD cell lines. Key parameters analyzed encompassed clinical outcomes, cancer stemness indices, neoantigen load, and epithelial-mesenchymal transition (EMT) signatures.

Results: Pan-cancer analysis revealed significant STC1 overexpression in 18/33 cancer types (54.5%), particularly in prostate adenocarcinoma (94% deep deletions). STC1 expression correlated with poor prognosis (HR=1.32, p<0.01), elevated TMB (r=0.43), and MSI (r=0.38) across multiple malignancies. Single-cell RNA sequencing demonstrated strong EMT association (NES=2.18, FDR<0.001). In STAD, we confirmed 3.7-fold protein overexpression (p=0.008) and identified positive correlations with CD8+ T cell (r=0.62, p=0.002) and CD4+ T cell infiltration (r=0.58, p=0.004).

Conclusion: This multi-modal study establishes STC1 as a novel pan-oncogenic factor with dual roles in tumor progression (via EMT and stemness regulation) and immune microenvironment remodeling. The strong association with immune checkpoints (PD-L1, CTLA4) and T cell infiltration patterns positions STC1 as a promising immunotherapeutic target, particularly in STAD and MSI-high cancers. Our findings provide mechanistic insights for developing STC1-directed therapeutic strategies.