Elevated levels of urinary PGE-M are found in tobacco users and indicate a poor prognosis for oral squamous cell carcinoma patients

Abstract

Cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) plays a role in the development and progression of epithelial malignancies.Measurements of urinary PGE-M, a stablemetabolite of PGE2, reflect systemic PGE2 levels.Here, we investigatedwhether urinary PGE-M levels were elevated in healthy tobacco users and in patients with oral squamous cell carcinoma (OSCC). Median urinary PGE-M levels were increased in healthy tobacco quid chewers [21.3 ng/mgcreatinine (Cr); n=33; P=0.03] and smokers (32.1 ng/mg Cr; n =31; P < 0.001) compared with never tobacco quid chewers-never smokers (18.8 ng/mg Cr; n =30). Urinary PGE-M levels were also compared in OSCC patients versus healthy tobacco users. An approximately 1-fold increase inmedian urinary PGE-M level was found in OSCC patients (48.7 ng/mg Cr, n =78) versus healthy controls (24.5 ng/mg Cr, n =64; P < 0.001). We further determined whether baseline urinary PGE-M levels were prognostic in OSCC patients who underwent treatment with curative intent.A nearly 1-fold increase in baseline urinaryPGE-M levels (64.7 vs. 33.8 ng/mg Cr, P < 0.001) was found in the group of OSCC patients who progressed (n =37) compared with the group that remained progression free (n=41). Patients with high baseline levels of urinary PGE-M had both worse disease-specific survival [HR, 1.01 per unit increase; 95% confidence interval (CI), 1.01- 1.02; P < 0.001] and overall survival (HR, 1.01 per unit increase; 95% CI, 1.00-1.02; P =0.03). Taken together, our findings raise the possibility that NSAIDs, prototypic inhibitors of PGE2 synthesis, may be beneficial for reducing the risk of tobacco-related aerodigestive malignancies or treating OSCC patients with high urinary PGE-M levels. Cancer Prev Res; 9(6); 428-36.