A core gene network linking developmental signaling and immune response in stomach adenocarcinoma revealed by integrated bioinformatics

Objective This study aims to identify and characterize the core gene network that molecularly integrates developmental signaling pathways with immune responses in stomach adenocarcinoma (STAD), and to evaluate the clinical relevance of the key hub genes within this network as potential prognostic biomarkers and therapeutic targets. Methods We analyzed the TCGA-STAD dataset to identify differentially expressed genes. Protein-protein interaction (PPI) networks were constructed using Cytoscape, and hub genes were screened based on betweenness centrality. High-confidence interactions were extracted from the STRING database. Functional enrichment analysis was performed using GO and KEGG. Clinical relevance was validated through survival analysis and stage-expression correlation. Results From 230 differentially expressed genes, we identified 46 core genes through multi-step screening. Functional enrichment revealed their significant involvement in developmental processes and immune-inflammatory responses. Eight key hub genes (TNF, IL17A, IFNG, SHH, BMP2, ULBP2, JUN, CXCL10) demonstrated significant prognostic value. High expression of TNF, IL17A, and SHH was associated with poor prognosis, whereas IFNG, JUN, and CXCL10 predicted favorable outcomes. ULBP2 exhibited progressive upregulation with advancing tumor stage, suggesting its role in disease progression. Conclusion We identified a core gene network that functionally integrates developmental programming with immune regulation in STAD. This network provides a framework for understanding disease heterogeneity and offers potential biomarkers for prognosis prediction and therapeutic targeting.