15-PGDH Expression in Gastric Cancer: A Potential Role in Anti-Tumor Immunity.

Introduction: Host immunity plays a vital role in tumorigenesis, including in tumor invasion and metastasis. However, the precise underlying mechanism remains to be explored. The enzyme 15-PGDH, which plays a key role in prostaglandin degradation, is a critical inflammatory mediator in gastric cancer (GC) tumorigenesis.

Materials And Methods: Immunohistochemistry was performed to determine 15-PGDH expression in GC and the corresponding adjacent non-neoplastic tissues (n=92).

Results: The expression of 15-PGDH in GC tissues was significantly lower than that in paracancerous tissues (<0.001) and found to correspond inversely with GC differentiation (0.043) and lymph node metastasis (0.046). In contrast, FOXP3 expression was increased in poorly differentiated GC tissues (0.001). Kaplan-Meier analysis revealed that GC patients with low expression of 15-PGDH (Log rank test, 0.007) and high expression of FOXP3 (Log rank test, 0.009) had shorter overall survival (OS) than those with high 15-PGDH and low FOXP3 expression. OS was also correlated with pathological tumor-node-metastasis stage (Log rank test, 0.014). Furthermore, using Cox proportional hazard regression, 15-PGDH expression [hazard ratio (HR): 0.605 (0.440-0.833); 0.002] was identified as an independent factor for OS.

Conclusion: Our data suggest that 15-PGDH may contribute to anti-tumor immunity by regulating FOXP3 Treg cells. The findings are useful for the identification of therapeutic targets for the management of GC.