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 stable metabolite of PGE2, reflect systemic PGE2 levels. Here, we investigated whether 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/mg creatinine (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 in median 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 urinary PGE-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. ©2016 AACR.

• Authors: Vikram D Kekatpure, Naveen Bs, Hanhan Wang, Xi Kathy Zhou, Chandramohan Kandasamy, Sumsum P Sunny, Amritha Suresh, Ginger L Milne, Moni Abraham Kuriakose, Andrew J Dannenberg
• Journal: Cancer prevention research (Philadelphia, Pa.) (Cancer Prev Res (Phila)) Vol. 9 Issue 6 Pg. 428-36 (06 2016) ISSN: 1940-6215 [Electronic] United States
• PMID: 27045033 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2016 American Association for Cancer Research.

Chemical References

• Biomarkers, Tumor
• Prostaglandins
• 7-hydroxy-5,11-dioxotetranorprostane-1,16-dioic acid

Topics

• Adult
• Aged
• Biomarkers, Tumor (urine)
• Carcinoma, Squamous Cell (etiology, mortality, urine)
• Chromatography, Liquid
• Female
• Head and Neck Neoplasms (etiology, mortality, urine)
• Humans
• Kaplan-Meier Estimate
• Male
• Mass Spectrometry
• Middle Aged
• Mouth Neoplasms (etiology, mortality, urine)
• Prognosis
• Proportional Hazards Models
• Prostaglandins (urine)
• Smoking (adverse effects)
• Squamous Cell Carcinoma of Head and Neck