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 E 2 (PGE 2 ) plays a role in the development and progression of epithelial malignancies. Measurements of urinary PGE-M, a stable metabolite of PGE 2 , reflect systemic PGE 2 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 ¼ 33; P ¼ 0.03] and smokers (32.1 ng/mg Cr; n ¼ 31; P < 0.001) compared with never tobacco quid chewers-never smokers (18.8 ng/mg Cr; n ¼ 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 ¼ 78) versus healthy controls (24.5 ng/mg Cr, n ¼ 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 ¼ 37) compared with the group that remained progression free (n ¼ 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 ¼ 0.03). Taken together, our findings raise the possibility that NSAIDs, prototypic inhibitors of PGE 2 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. Ó2016 AACR.

Variation in prostaglandin metabolism during growth of the diatom Thalassiosira rotula

“…Bacteria are able to assimilate phosphate better than algae, especially at low concentrations 43 , and compete with algae for inorganic nutrients 44 . This increased pressure may stimulate PGs synthesis in diatoms as already shown in animals, where COX expression is stimulated in the presence of bacteria 45 and in humans where PGE 2 have been correlated to viral load and infection severity in influenza [46][47][48][49] . In line with this hypothesis, similar compounds, such as hydroxylated eicosapentaenoic acid 15-HEPE, were shown to be up-regulated and released from cells when the diatom S. marinoi was exposed to pathogenic bacteria 50 .…”

“…In line with this hypothesis, similar compounds, such as hydroxylated eicosapentaenoic acid 15-HEPE, were shown to be up-regulated and released from cells when the diatom S. marinoi was exposed to pathogenic bacteria 50 . PGE 2 is the most abundant prostanoid in the human body, but it is also very unstable since it is rapidly converted into PGE-M [46][47][48][49] that is considered to mirror the systemic levels of PGE 2 formation. In our study, PGE 2 was present at low levels in the medium during the exponential growth phase and was almost absent in the late stationary phase (from day 7) while PGE-M levels increased exponentially up to the senescent phase (Fig.…”

Metabolic Biomarkers of Squamous Cell Carcinoma of the Aerodigestive Tract: A Systematic Review and Quality Assessment

“…Reporting of clinical demographics was not consistent in each study. Of the 30 studies, only 10 fully reported all clinical demographics [28,30,34,35,38,41,43,47,49,51], 13 reported at least patient age, gender, and clinical stage [16,25,26,31,36,39,40,42,45,46,48,52,53]. Seven studies did not report differences in metabolite profile at different tumour stages [24,27,29,32,36,37,46].…”

“…Out of 30 studies, only 12 declared evidence of data preprocessing [25,29,33,34,36,37,40,41,43,45,48,49]. Levels one, two, and three metabolite identification were reported in nine [25,27,30,32,36,39,40,46,52], 15 [16,24,26,29,33,34,37,42,43,45,47,49,51,56,58], and six [28,31,35,38,41,48] studies, respectively. Only two of the 30 studies reported all of the statistical aspects suggested by the CAWG-MSI guidelines [59].…”

Repurposing existing medications in oncology and their potential role in oral cancer

“…Previous reports have suggested a correlation between expression of COX‐2, occurrence of oral cancer, and a worse prognosis (Wang et al., ). COX‐2 levels are induced by tobacco carcinogens (Kekatpure et al., ) and are observed at high levels in leukoplakias and primary and metastatic squamous carcinomas of the head and neck (Javed & Warnakulasuriya, ). Use of NSAIDs has been associated with a reduced risk of HNSCC in some epidemiologic studies (Ahmadi et al., ; Tang et al., ).…”