Levels of Prostaglandin E Metabolite, the Major Urinary Metabolite of Prostaglandin E2, Are Increased in Smokers

Abstract

Purpose: Increased levels of cyclooxygenase-2 and prostaglandin E 2 (PGE 2 ) have been observed in tobacco-related malignancies of the upper aerodigestive tract. Moreover, exposure to tobacco smoke can stimulate the synthesis of PGE 2 . Recent evidence suggests that urinary PGE metabolite (PGE-M) can be used as an index of systemic PGE 2 production. In this study, we investigated whether levels of urinary PGE-M were increased in smokers and in patients with head and neck squamous cell carcinoma (HNSCC). Experimental Design: Fifty-eight HNSCC cases and 29 age-and gender-matched healthy controls were prospectively enrolled in the study. A detailed smoking history and single void urine specimen were obtained from each participant. Levels of urinary PGE-M were quantified in a blinded fashion using mass spectrometry and compared with smoking history and tumor status. Results: Adjusted for case-control matching, median urinary PGE-M levels were significantly higher in ever smokers (15.7 ng/mg creatinine) compared with never smokers (9.9 ng/mg creatinine) for the entire study population (n = 87, P = 0.005). Concentrations of urinary PGE-M were nearly doubled in ever smokers (15.2 ng/mg creatinine) versus never smokers (7.8 ng/mg creatinine) among healthy controls (P = 0.001). Higher PGE-M levels were observed in current versus former smokers and in those with greater pack-year exposure. A significant difference in amounts of PGE-M was not observed in patients with HNSCC versus healthy controls. Conclusions: Increased levels of urinary PGE-M were observed in smokers. Urinary PGE-M may have use as a noninvasive biomarker of the effects of tobacco smoke exposure.

A simple and robust UPLC-SRM/MS method to quantify urinary eicosanoids

“…We found signifi cantly elevated levels of urinary tetranor PGE-M (metabolite of PGE 2 ), both PGF 2 metabolites 2,3-dinor-8-iso-and 8-iso-PGF 2 ␣ , and 2,3-dinor-TXB 2 (metabolite of TXA 2 ). These results are in good agreement with fi ndings from other groups ( 33,36,38,51 ). Levels of 11-dehydro-TXB 2 (also a metabolite of TXA 2 ) were similar in urine of smokers and nonsmokers, which is somewhat surprising because elevated levels for smokers have been reported previously ( 52 ).…”

Elevated Levels of Urinary PGE-M Are Found in Tobacco Users and Indicate a Poor Prognosis for Oral Squamous Cell Carcinoma Patients

“…We also found increased urinary PGE-M in OSCC patients in comparison with healthy tobacco users. Previously, we found a near statistically significant increase in urinary PGE-M in HNSCC patients (45). The fact that the effects were more dramatic in the current study is likely to reflect differences in study design.…”

“…The current study was larger than the original one and limited to patients with OSCC. Moreover, in the original HNSCC study, the patient population was more heterogeneous and included multiple tumor sites including the larynx and paranasal sinuses (45). The observed elevation in urinary PGE-M fits with the known elevation of PGE 2 in HNSCC (5,16).…”

Thematic Review Series: Proteomics. An integrated omics analysis of eicosanoid biology

“…In addition to reducing PGs, 13-PGR has been shown to use lipoxins as substrates (234). The resulting metabolites from 13-PGR activity show reduced biological activity, and PGE 2 metabolites from this pathway are readily detected in urinary excretion (235). The rat protein has LTB 4 DH and 13-PGR activities, suggesting that these funcAn integrated omics analysis of eicosanoid biology 1029 by guest, on April 29, 2019 www.jlr.org Downloaded from tions are retained in the murine homolog (see supplementary Table VI).…”