Urinary levels of prostaglandin E2 are positively correlated with intratumoral infiltration of Foxp3+ regulatory T cells in non-small cell lung cancer

The immune microenvironment of primary tumors has been reported to be one of the factors influencing the prognosis of patients with cancer. The tumor-infiltrating regulatory T cell (Treg) count has previously been revealed to be positively correlated with intratumoral cyclooxygenase-2 (Cox-2) expression, and was also associated with poor survival among patients with non-small cell lung cancer (NSCLC). In addition, the urinary levels of a prostaglandin E2 (PGE2) metabolite (PGE-M) were used as a biomarker in clinical trials of the Cox-2 inhibitor celecoxib. In the current prospective study, the association of urinary PGE2 and PGE-M levels with intratumoral Cox-2 expression and Treg count was examined in patients with NSCLC. A total of 21 patients with NSCLC who underwent complete resection of the tumor at Kawasaki Medical School Hospital (Kurashiki, Japan) were enrolled. Urine specimens were obtained prior to surgery in order to examine urinary PGE2 and PGE-M levels. A significant positive association was observed between urinary PGE2 levels and the intratumoral Treg count (P=0.023), but not the intratumoral Cox-2 expression levels. No significant associations were identified between urinary PGE2 levels and any of the other clinicopathological characteristics examined, including age, sex, smoking history, histology, tumor size, nodal status and disease stage. However, no significant association was observed between urinary PGE-M levels and the intratumoral Treg count (P=0.069) or Cox-2 expression. In conclusion, urinary PGE2 levels were positively correlated with intratumoral Treg counts in patients with NSCLC in the current study. This indicates that urinary PGE2 may be an improved biomarker, compared with PGE-M, for the prediction of intratumoral Treg numbers.