Objective We assessed COL4A2 expression in stomach adenocarcinoma (STAD) for correlations with the disease's clinical features and immune cell infiltration.

Methods The target gene COL4A2 was identified through bioinformatics screening. Database analysis was then conducted to investigate its mRNA expression, clinical significance, prognostic value, and relationship with immune cell infiltration in STAD. A retrospective review of clinical data from 60 patients diagnosed with STAD at Shanxi Province Cancer Hospital between August and November 2022 was conducted. Immunohistochemistry (IHC) was used to detect COL4A2 protein expression in cancer tissues, and its expression levels were investigated for correlations with patients' clinicopathological characteristics. IHC analysis was performed to detect MMP2, HER2, MMR, immune cell marker, and inhibitory immune checkpoint protein expression in STAD tissue. Correlations between these indicators and COL4A2 protein expression levels were also analyzed.

Results Bioinformatics analysis revealed that COL4A2 mRNA expression is significantly upregulated in STAD (P=0.003), and its expression level significantly correlates with T staging and overall patient survival (P<0.05). IHC results confirmed that COL4A2 protein was significantly overexpressed in STAD and correlated positively with TNM staging, MMP2 expression levels, and CD4⁺/CD8⁺ T cell infiltration. Its overexpression also associated with upregulation of immunosuppressive checkpoints such as PD-1 and TIM-3 (P<0.05). This association provides preliminary evidence suggesting potential involvement of COL4A2 in regulating the tumor immune microenvironment.

Conclusions COL4A2 displays potential to act as an immune-related regulatory molecule. However, whether it can serve as a biomarker to predict immunotherapy efficacy or as a guide for combination therapy requires further validation through functional experiments and clinical studies with larger sample sizes.