High expression of SENP1 correlates with poor prognosis and immune evasion in gastric cancer.

Gastric cancer (GC) remains a highly prevalent malignancy with poor prognosis in advanced stages. SUMOylation, a key post-translational modification, regulates tumor progression and immune responses, yet the role of SUMO-specific protease 1 (SENP1) in GC remains unclear. Here, we show that SENP1 is significantly overexpressed in GC tissues and cell lines, as demonstrated by analyses of TCGA/GEO datasets and by immunohistochemistry, western blotting, and qRT-PCR. Higher SENP1 levels were associated with more advanced disease, undifferentiated histology, systemic dissemination, and worse survival. Functionally, either SENP1 knockdown or its pharmacological inhibition with Momordin Ic impaired gastric cancer cell proliferation and migration, induced apoptosis, and caused cell cycle arrest. Complementary enrichment and immune-infiltration analyses link higher SENP1 expression to tumor-promoting pathways, upregulation of immune-checkpoint genes (PD-L1, PD-1, CTLA4), and reduced microsatellite instability, suggesting a role in immune evasion. Collectively, these findings identify SENP1 as a prognostic marker and potential therapeutic target in GC, with putative involvement in both tumor progression and modulation of the tumor immune microenvironment.