Prognostic implications of prostaglandin E-major urinary metabolite in resected non-small-cell lung cancer

Abstract

OBJECTIVES Cyclooxygenase-2-derived prostaglandin E2 (PGE2) is highly involved in the promotion of cancer progression. The end product of this pathway, PGE-major urinary metabolite (PGE-MUM), is a stable metabolite of PGE2 that can be assessed non-invasively and repeatedly in urine samples. The aim of this study was to assess the dynamic changes in perioperative PGE-MUM levels and their prognostic significance in non-small-cell lung cancer (NSCLC). METHODS Between December 2012 and March 2017, 211 patients who underwent complete resection for NSCLC were analysed prospectively. PGE-MUM levels in 2 spot urine samples taken 1 or 2 days preoperatively and 3–6 weeks postoperatively were measured using a radioimmunoassay kit. RESULTS Elevated preoperative PGE-MUM levels were associated with tumour size, pleural invasion and advanced stage. Multivariable analysis revealed that age, pleural invasion, lymph node metastasis and postoperative PGE-MUM levels were independent prognostic factors. In matched pre- and postoperative urine samples obtained from patients who are eligible for adjuvant chemotherapy, an increase in PGE-MUM levels following resection was an independent prognostic factor (hazard ratio 3.017, P = 0.005). Adjuvant chemotherapy improved survival in patients with increased PGE-MUM levels after resection (5-year overall survival, 79.0 vs 50.4%, P = 0.027), whereas survival benefit was not observed in those with decreased PGE-MUM levels (5-year overall survival, 82.1 vs 82.3%, P = 0.442). CONCLUSIONS Increased preoperative PGE-MUM levels can reflect tumour progression and postoperative PGE-MUM levels are a promising biomarker for survival after complete resection in patients with NSCLC. Perioperative changes in PGE-MUM levels may aid in determining the optimal eligibility for adjuvant chemotherapy.

Prostaglandin E-major urinary metabolites as a new biomarker for acute mesenteric ischemia

“…Therefore, the utility of PGE-MUM is also suggested in conditions related to the COX-2 enzyme, such as lung adenocarcinoma, interstitial pneumonia, and mesenteric adipose inflammation. [23][24][25] In the present study, the SMAO group showed higher PGE-MUM levels than the sham group. Furthermore, even when the duration of reperfusion was the same, the duration of ischemia correlated with higher PGE-MUM levels, suggesting a potential correlation between the degree of intestinal ischemia and PGE-MUM levels independent of reperfusion.…”

“…Our study showed that intestinal ischemia is associated with PGE-MUM when studied using a rat intestinal ischemia model. Although most reports on PGE-MUM are based on human data, 8,[12][13][14][15][20][21][22][23][24][25] studies to determine the validity of PGE-MUM measurements in rodents after the induction of intestinal ischemia/necrosis are lacking. In the current study, we demonstrated the validity of the PGE-MUM test in rat samples using dilution linearity testing.…”

“…Previous reports have suggested a correlation between PGE-MUM elevation and UC through a mechanism that involves an increase in PGE2. Therefore, the utility of PGE-MUM is also suggested in conditions related to the COX-2 enzyme, such as lung adenocarcinoma, interstitial pneumonia, and mesenteric adipose inflammation 23–25 …”