Urine PGE-M: A metabolite of prostaglandin E2 as a potential biomarker of advanced colorectal neoplasia.
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.
Johnson
J Chad
JC
Department of Surgery, Vanderbilt University, Nashville, Tennessee, USA.
Schmidt
Carl R
CR
Shrubsole
Martha J
MJ
Billheimer
D Dean
DD
Joshi
Prashant R
PR
Morrow
Jason D
JD
Heslin
Martin J
MJ
Washington
M Kay
MK
Ness
Reid M
RM
Zheng
Wei
W
Schwartz
David A
DA
Coffey
Robert J
RJ
Beauchamp
R Daniel
RD
Merchant
Nipun B
NB
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
D014408:Biomarkers, Tumor; D011453:Prostaglandins; C060526:7-hydroxy-5,11-dioxotetranorprostane-1,16-dioic acid; D051546:Cyclooxygenase 2