Work

The vesicle transport gene SEC23A is a novel prognostic indicator and therapeutic target in gastric cancer

Year: 2026

Type: article

Abstract: Objective SEC23A, a gene implicated in vesicle transport, has an undefined role in the progression of gastric cancer (GC). This study aims to comprehensively characterize the clinical significance, molecular mechanisms, and therapeutic potential of SEC23A in GC. Methods We systematically analyzed SEC23A expression and its prognostic value in GC cohorts from The Cancer Genome Atlas and Gene Expression Profiling Interactive Analysis. Genetic alterations were assessed using cBioPortal. Functional networks, including competitive endogenous RNA and protein-protein interaction networks, were constructed. The tumor immune microenvironment was evaluated using the Tumor Immune Estimation Resource 2.0, CIBERSORT, and single-sample gene set enrichment analysis. Drug sensitivity was predicted using data from The Cancer Immunome Atlas and the R package “pRRophetic”. Key findings were validated with data from the Gene Expression Omnibus and the Human Protein Atlas. In vitro functional assays were conducted to assess the impact of SEC23A knockdown on GC cell proliferation. Results Overexpression of SEC23A was significantly associated with poor overall survival in GC patients, particularly in those with undifferentiated tumors. Functionally, high SEC23A levels promoted tumor cell proliferation and were correlated with an immunosuppressive microenvironment, characterized by increased M2 macrophage infiltration and reduced Tregs. Patients with high SEC23A expression exhibited reduced sensitivity to anti-PD-1/CTLA-4 immunotherapy but showed heightened sensitivity to certain small-molecule inhibitors. Consistent with these observations, in vitro experiments confirmed that SEC23A knockdown effectively suppressed GC cell proliferation. Conclusions Our findings underscore the critical role of SEC23A in driving GC progression and modulating the immune landscape. SEC23A represents a promising prognostic biomarker and a novel therapeutic target for GC, potentially guiding strategies involving immunotherapy and small-molecule inhibitors.

Source: Frontiers in Oncology

DOI: 10.3389/fonc.2026.1728472