Prostaglandin E-major urinary metabolite as a reliable surrogate marker for mucosal inflammation in ulcerative colitis.
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.
*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.
Yoshinori
Y
Arai
Seiji
S
Arihiro
Tomokazu
T
Matsuura
Tomohiro
T
Kato
Mika
M
Matsuoka
Masayuki
M
Saruta
Makoto
M
Mitsunaga
Masaaki
M
Matsuura
Mutsunori
M
Fujiwara
Isao
I
Okayasu
Satoru
S
Ito
Hisao
H
Tajiri
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D002097:C-Reactive Protein / Q000378:metabolism; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000503:physiopathology*; D003113:Colonoscopy / Q000379:methods; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D018078:Receptors, Prostaglandin E / Q000378:metabolism*; D018570:Risk Assessment; D012720:Severity of Illness Index; D055815:Young Adult
D015415:Biomarkers; D018078:Receptors, Prostaglandin E; D002097:C-Reactive Protein