title: Urine PGE-M: A metabolite of prostaglandin E2 as a potential biomarker of advanced colorectal neoplasia.
abstract: OBJECTIVE
  The enzyme cyclooxygenase-2 is expressed in a majority of colorectal carcinomas (CRCs) and is important in prostaglandin production. We have developed an accurate method to measure the urinary metabolite of prostaglandin E(2) (PGE-M) using recently developed mass spectrometric techniques. The purpose of this pre-validation study was to determine if urinary PGE-M levels can be used as a biomarker to discriminate between healthy patients and those with colorectal disease.
  
  
  METHODS
  Urine PGE-M was assessed in a total of 228 patients with CRC, colonic adenomatous polyps, Crohn's disease, and in subjects with no endoscopically detectable disease. Thirteen rectal carcinoma patients were treated with celecoxib and urinary PGE-M was measured before and after treatment.
  
  
  RESULTS
  Urine PGE-M levels were increased among healthy men compared with healthy women (median, 8.59 [interquartile range (IQR), 5.67-22.3] vs 4.25 [IQR, 2.35-6.03], P = .0027). Urine PGE-M levels among patients with Crohn's disease (median, 19.85 [IQR, 6.89-90.2]), CRC (median, 14.65 [IQR, 5.94-92.1]), or large adenomas greater than 1 cm in size (median, 18.85 [IQR, 11.9-25.6]) were significantly increased when compared with patients who had either small polyps less than 1 cm in size (median, 9.69 [IQR, 6.41-22.2]), or no polyps (median, 7.05 [IQR, 2.35-24.7]) (P = .0001). PGE-M levels decreased significantly after celecoxib treatment in patients with rectal cancer (median, 21.7 [IQR, 16.2-29.9] vs 9.14 [IQR, 7.14-13.2], P = .009).
  
  
  CONCLUSIONS
  The increase in urinary PGE-M in patients with colorectal cancers and large adenomas suggests that urinary PGE-M is a potentially useful biomarker for the detection of advanced colorectal neoplasia.
authors.affiliation: Department of Surgery, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: J Chad
authors.initials: JC
authors.lastname: Johnson
authors.forename: Carl R
authors.initials: CR
authors.lastname: Schmidt
authors.forename: Martha J
authors.initials: MJ
authors.lastname: Shrubsole
authors.forename: D Dean
authors.initials: DD
authors.lastname: Billheimer
authors.forename: Prashant R
authors.initials: PR
authors.lastname: Joshi
authors.forename: Jason D
authors.initials: JD
authors.lastname: Morrow
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Heslin
authors.forename: M Kay
authors.initials: MK
authors.lastname: Washington
authors.forename: Reid M
authors.initials: RM
authors.lastname: Ness
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: David A
authors.initials: DA
authors.lastname: Schwartz
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Coffey
authors.forename: R Daniel
authors.initials: RD
authors.lastname: Beauchamp
authors.forename: Nipun B
authors.initials: NB
authors.lastname: Merchant
mesh_terms: D000236:Adenoma / Q000175:diagnosis; D000368:Aged; D014408:Biomarkers, Tumor; D003111:Colonic Polyps / Q000175:diagnosis; D015179:Colorectal Neoplasms / Q000175:diagnosis*; D003424:Crohn Disease / Q000175:diagnosis / Q000652:urine; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011453:Prostaglandins / Q000652:urine*; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D011453:Prostaglandins; C060526:7-hydroxy-5,11-dioxotetranorprostane-1,16-dioic acid; D051546:Cyclooxygenase 2