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15-PGDH Expression in Gastric Cancer: A Potential Role in Anti-Tumor Immunity
Yaling Li1,2,3, Junjie Li1, Juanjuan Dong1
1Provincial-Level Key Laboratory of Molecular Medicine of Major Diseases and Study on Prevention and Treatment of Traditional Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu, People's Republic of China.
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 (P<0.001) and found to correspond inversely with GC differentiation (P=0.043) and lymph node metastasis (P=0.046). In contrast, FOXP3 expression was increased in poorly differentiated GC tissues (P=0.001). Kaplan-Meier analysis revealed that GC patients with low expression of 15-PGDH (Log rank test, P=0.007) and high expression of FOXP3 (Log rank test, P=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, P=0.014). Furthermore, using Cox proportional hazard regression, 15-PGDH expression [hazard ratio (HR): 0.605 (0.440-0.833); P=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.
