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Prostaglandin EMajor Urinary Metabolite as a Reliable Surrogate Marker for Mucosal Inflammation in Ulcerative Colitis

Arai, Yoshinori MD*; Arihiro, Seiji MD, PhD*; Matsuura, Tomokazu MD, PhD; Kato, Tomohiro MD, PhD; Matsuoka, Mika MD, PhD*; Saruta, Masayuki MD, PhD*; Mitsunaga, Makoto MD, PhD*; Matsuura, Masaaki PhD§; Fujiwara, Mutsunori MD, PhD; Okayasu, Isao MD, PhD; Ito, Satoru PhD**; Tajiri, Hisao MD, PhD*,‡

doi: 10.1097/MIB.0000000000000062
Original Clinical Articles

Background: C-reactive protein (CRP) is used as a biomarker of ulcerative colitis (UC) activity, but CRP levels are sometimes insufficient to reflect UC activity. Therefore, a simple noninvasive biomarker assay with sufficient sensitivity and specificity to accurately reflect UC activity is desired. Since prostaglandin E2 production and colonic inflammation are associated, we evaluated whether prostaglandin E–major urinary metabolite (PGE-MUM) can be used as such a biomarker.

Methods: Patients with UC (n = 99) were enrolled from March 2011 to February 2012. UC activity was evaluated using the simple clinical colitis activity index in 99 patients, Mayo endoscopic scoring (Mayo) in 79 patients, and Matts' grading (Matts) in 64 patients. PGE-MUM levels were measured by radioimmunoassay kit and compared against CRP levels as a control.

Results: Both PGE-MUM and CRP levels correlated with UC activity (P < 0.01). Areas under the receiver operating characteristic curves of simple clinical colitis activity index, Mayo, and Matts for PEG-MUM were each higher than for CRP (0.93 > 0.73, 0.90 > 0.77, and 0.89 > 0.75, respectively). In multivariate logistic regression models, PGE-MUM was a significant independent predictor of histologic remission (sensitivity/specificity, 0.82/0.82) when the cutoff value was set to 17.0 μg/g creatinine, but CRP was not (0.69/0.69) (P < 0.01).

Conclusions: Compared with CRP level, PGE-MUM level demonstrated better sensitivity for reflecting UC activity, especially in cases of histologic inflammation, and thus seems to be a better evaluator of mucosal healing. Because this method is simple, quick, and noninvasive, PGE-MUM seems to be a useful biomarker of UC.

Article first published online 19 May 2014.

*Division of Gastroenterology and Hepatology, Department of Internal Medicine,

Departments of Laboratory Medicine, and

Endoscopy, The Jikei University School of Medicine, Tokyo, Japan;

§Division of Cancer Genomics, Cancer Institute of JFCR and Bioinformatics Group, Genome Center of JFCR, Japanese Foundation for Cancer Research, Tokyo, Japan;

Department of Clinical Pathology, Japanese Red Cross Medical Center, Tokyo, Japan;

Department of Pathology, Kitasato University School of Medicine, Kanagawa, Japan; and

**Department of Scientific Information, Fujirebio, Inc, Tokyo, Japan. Ito is now with the IDAC Theranostics, Inc., University of Tokyo Entrepreneur Plaza, Tokyo, Japan.

Reprints: Seiji Arihiro, MD, PhD, Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo 105-8461, Japan (e-mail: sarihiro@gmail.com).

The prostaglandin E–major urinary metabolite measurement kit was kindly provided by TFB, Inc (Tokyo, Japan).

The authors have no conflicts of interest to disclose.

Received March 14, 2014

Accepted March 31, 2014

© Crohn's & Colitis Foundation of America, Inc.
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