title: 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.affiliation: Department of Head and Neck Oncology, Mazumdar-Shaw Cancer Center, Narayana Health, Health City, Bangalore, India. Department of Medicine, Weill Cornell Medical College, New York, New York. kvikram2000@gmail.com ajdannen@med.cornell.edu.
authors.forename: Vikram D
authors.initials: VD
authors.lastname: Kekatpure
authors.affiliation: Department of Head and Neck Oncology, Mazumdar-Shaw Cancer Center, Narayana Health, Health City, Bangalore, India.
authors.forename: Naveen
authors.initials: N
authors.lastname: Bs
authors.affiliation: Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, New York.
authors.forename: Hanhan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, New York.
authors.forename: Xi Kathy
authors.initials: XK
authors.lastname: Zhou
authors.affiliation: Syngene International Limited, Bengaluru, India.
authors.forename: Chandramohan
authors.initials: C
authors.lastname: Kandasamy
authors.affiliation: Department of Head and Neck Oncology, Mazumdar-Shaw Cancer Center, Narayana Health, Health City, Bangalore, India. Mazumdar-Shaw Center for Translational Research, Bangalore, India.
authors.forename: Sumsum P
authors.initials: SP
authors.lastname: Sunny
authors.affiliation: Department of Head and Neck Oncology, Mazumdar-Shaw Cancer Center, Narayana Health, Health City, Bangalore, India. Mazumdar-Shaw Center for Translational Research, Bangalore, India.
authors.forename: Amritha
authors.initials: A
authors.lastname: Suresh
authors.affiliation: Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Ginger L
authors.initials: GL
authors.lastname: Milne
authors.affiliation: Department of Head and Neck Oncology, Mazumdar-Shaw Cancer Center, Narayana Health, Health City, Bangalore, India.
authors.forename: Moni Abraham
authors.initials: MA
authors.lastname: Kuriakose
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, New York. kvikram2000@gmail.com ajdannen@med.cornell.edu.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Dannenberg
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000652:urine*; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000401:mortality / Q000652:urine*; D002853:Chromatography, Liquid; D005260:Female; D006258:Head and Neck Neoplasms / Q000209:etiology / Q000401:mortality / Q000652:urine*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000209:etiology / Q000401:mortality / Q000652:urine*; D011379:Prognosis; D016016:Proportional Hazards Models; D011453:Prostaglandins / Q000652:urine*; D012907:Smoking / Q000009:adverse effects*; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D014408:Biomarkers, Tumor; D011453:Prostaglandins; C060526:7-hydroxy-5,11-dioxotetranorprostane-1,16-dioic acid