<p>15-PGDH Expression in Gastric Cancer: A Potential Role in Anti-Tumor Immunity</p>

Abstract

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.

Comparative proteomics analysis in different stages of urothelial bladder cancer for identification of potential biomarkers: highlighted role for antioxidant activity

“…Finally, we identified the up-regulation of PGDH in MIBC tissues. As demonstrated in several studies, the expression of the PGDH has been significantly decreased in various types of cancer tissues which assuming to act as a potential tumor suppressor by inhibiting proliferation and differentiation of cancer cells [ 72 – 74 ]. While most reports revealed low expression levels of PGDH in different cancers, high expression levels of PGDH have been observed in ovarian cancer [ 75 ].…”

The Role of Prostaglandins in Different Types of Cancer

“…The enzyme 15-PGDH, which plays a key role in prostaglandin degradation, is a critical inflammatory mediator in gastric cancer tumorigenesis. A study with gastric carcinoma patients demonstrated that 15-PGDH may contribute to anti-tumor immunity by regulating FOXP3 (fork head box protein 3) [63]. Also, a study with 277 patients showed that the presence of the prostaglandin PGD 2 reduces tumor expansion of gastric adenocarcinoma by inhibiting the peroxisome proliferator-activated receptor gamma (PPARγ) pathway [36].…”

Overexpression of 15-Hydroxyprostaglandin Dehydrogenase Inhibits A549 Lung Adenocarcinoma Cell Growth via Inducing Cell Cycle Arrest and Inhibiting Epithelial-Mesenchymal Transition

“…14 For breast cancer and gastric cancer patients, the low expression of 15-PGDH is associated with reduced overall survival. 16,17 In addition, the expression level of 15-PGDH is associated with drug resistance. 16 The down-regulated expression level of 15-PGDH is related to tamoxifen resistance and decreases overall survival in ERα-positive breast cancer patients.…”