Increased Levels of Urinary PGE-M, a Biomarker of Inflammation, Occur in Association with Obesity, Aging, and Lung Metastases in Patients with Breast Cancer

Abstract

Elevated levels of cyclooxygenase (COX)-derived prostaglandin E2 (PGE2) occur in inflamed tissues. To evaluate the potential links between inflammation and breast cancer, levels of urinary prostaglandin E-metabolite (PGE-M), a stable end metabolite of PGE2, were quantified. We enrolled 400 patients with breast cancer: controls with early breast cancer (n=200), lung metastases (n=100) and metastases to other sites (n=100). Patients completed a questionnaire, provided urine and had measurements of height and weight. Urinary PGE-M was quantified by mass spectrometry. Ever smokers with lung metastasis who had not been exposed to NSAIDs had the highest PGE-M levels. PGE-M levels were increased in association with elevated BMI (p<0.001), aging (p<0.001), pack-year smoking history (p=0.02), lung metastases (p=0.02) and recent cytotoxic chemotherapy (p=0.03). Conversely, use of NSAIDs, prototypic inhibitors of COX activity, was associated with reduced PGE-M levels (p<0.001). Based on the current findings, PGE-M is likely to be a useful biomarker for the selection of high risk subgroups to determine the utility of interventions that aim to reduce inflammation and possibly the development and progression of breast cancer, especially in overweight and obese women.

Urinary levels of prostaglandin E2 are positively correlated with intratumoral infiltration of Foxp3+ regulatory T cells in non-small cell lung cancer

“…Previous studies have suggested that the majority of PGE 2 formed in vivo is derived from Cox-2 (24,25). Urinary PGE-M levels in healthy patients or patients with lung cancer are suppressed significantly by nonselective Cox inhibitors, including aspirin, and by Cox-2-selective inhibitors (25).…”

Obesity and Cancer Mechanisms: Tumor Microenvironment and Inflammation

“…[55][56][57][58] In addition, increased prostaglandin E2 metabolite in the urine is found in women who are obese and is associated with an increased risk of postmenopausal breast cancer. 59,60 This could be a consequence of increased COX-2 levels in inflamed fat. Thus, smoldering WAT inflammation and low-grade systemic inflammation are inexorably coupled, and each perpetuates the other.…”

Obesity and Cancer: Concepts and Challenges

“…This low grade, smoldering inflammation has been associated with cancer development and promotion [87]. Several inflammatory biomarkers are commonly increased in obese individuals and data suggests a positive correlation between their levels in blood (TNF-α; IL-6) [62] and urine (PGE 2 metabolites) [88] with development and/or progression of breast tumors. In the complex context of systemic inflammation, circulating chemokines are active not only in recruiting monocytes to adipose tissue, but also through the stimulation of macrophage proliferation in the fat pad [89] that contributes to a continuous positive feedback system for local WAT inflammation.…”