GATA Binding Protein 3 as a Diagnostic Biomarker and Immune Infiltrates Regulator in Stomach Adenocarcinoma

Introduction GATA3 is a transcription factor that regulates cell differentiation, proliferation, and immune function. While it is well recognized as a diagnostic marker in breast and urothelial cancers, but in stomach adenocarcinoma (STAD) remains unclear. This study aimed to investigate the expression, clinical significance, promoter methylation, immune infiltration, and genetic alterations of GATA3 in STAD using comprehensive bioinformatics approaches. To our knowledge, this is the first study to systematically evaluate GATA3 across multiple datasets in the context of gastric cancer.  Methods The analyses were conducted on publicly available datasets, including Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN), Kaplan-Meier plotter (KM Plotter), cBioPortal for Cancer Genomics, and Gene Expression Omnibus (GEO). Results Our results revealed that GATA3 is significantly upregulated across multiple cancer types, with the highest expression observed in STAD (p < 0.001). According to cancer stages I-IV, the expression increased in stages II-III but declined in stage IV, suggesting a role in tumor progression. However, survival analyses across several platforms consistently demonstrated no significant association between GATA3 expression and overall survival (p > 0.05). Immune infiltration analysis showed strong correlations between GATA3 expression and CD8+ T cells, CD4+ T cells, and macrophages (p < 0.0001), highlighting its potential involvement in shaping the tumor immune microenvironment. Interestingly, despite its upregulation, GATA3 exhibited elevated promoter methylation, suggesting additional regulatory mechanisms beyond epigenetics. Genetic alterations were rare (4%) and did not impact survival outcomes. Conclusion Collectively, these findings suggest that GATA3 is significantly upregulated in STAD and may serve as a novel diagnostic marker associated with immune infiltration. The study provides a foundation for future research exploring GATA3 as a potential target for diagnostic development and immunotherapy strategies in gastric cancer.