Abstract
Background: Prostaglandin E2 (PGE2) is metabolized to prostaglandin E-major urinary metabolite (PGE-MUM). Enhanced cyclooxygenase-2 (COX-2) expression demonstrated in lung adenocarcinoma indicates increased PGE-MUM levels in patients with lung adenocarcinoma. Objectives: We aimed to elucidate the clinical usefulness of measuring PGE-MUM as an indicator of tumor burden in patients with lung adenocarcinoma. Methods: PGE-MUM was measured by a radioimmunoassay in control healthy volunteers (n = 124) and patients with lung adenocarcinoma (n = 54). Associations between PGE-MUM levels and clinical characteristics of the patients (including lung cancer stage and TNM factors (T: Tumor, N: Node, M: Metastasis) were examined. Results: PGE-MUM levels were significantly elevated in patients with lung adenocarcinoma. A PGE-MUM level of 14.9 μg/g∙Cr showed 70.4% sensitivity and 67.7% specificity for the diagnosis of lung adenocarcinoma. PGE-MUM levels tended to be positively correlated with cancer progression as determined by the TNM staging system. Advanced stage (stage III, stage IV, and recurrence) was significantly associated with high PGE-MUM levels by logistic regression analysis. No apparent correlation was demonstrated between PGE-MUM and carcinoma embryonic antigen (CEA) levels. Conclusions: PGE-MUM can be a promising biomarker reflecting the systemic tumor burden of lung adenocarcinoma.
Highlights
Lung cancer is one of the leading causes of death worldwide, and cigarette smoking is the main risk factor for lung cancer [1]
There was no difference in the sex ratio between the control group and the lung adenocarcinoma group
BMI was higher in the lung adenocarcinoma group; 55.6% of lung adenocarcinoma group had smoking history
Summary
Lung cancer is one of the leading causes of death worldwide, and cigarette smoking is the main risk factor for lung cancer [1]. Prostaglandin E2 (PGE2) is synthesized by cyclooxygenase (COX) and metabolized to stable prostaglandin E-major urinary metabolite 7alpha-hydroxy-5,11-diketotetranor-prosta-1,16-dioic acid (PGE-MUM) [3]. COX-2 is involved in lung tumorigenesis in mouse models, and PGE2 has been shown to promote proliferation and invasion of cancer cells [4,5,6]; the COX-2/PGE2 pathway can be of great importance in cancer patients who have elevated COX-2 levels. To evaluate the COX-2/PGE2 pathway, a reproducible method for measuring stable PGE-MUM using a simple radioimmunoassay kit was recently developed. The clinical usefulness of PGE-MUM measured by this kit as a biomarker showing disease activity has been demonstrated in inflammatory bowel disease [7] and chronic fibrotic lung disease [8]. Enhanced cyclooxygenase-2 (COX-2) expression demonstrated in lung adenocarcinoma indicates increased PGE-MUM levels in patients with lung adenocarcinoma
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