Potential usefulness of detecting cyclooxygenase 2 messenger RNA in feces for colorectal cancer screening.
OBJECTIVE
Cyclooxygenase 2 (COX-2) is overexpressed frequently in aerodigestive tumors, especially in colorectal tumors. Therefore, it may be a suitable biomarker for colorectal cancer (CRC) screening. We performed a pilot study of whether detecting COX-2 expression in fecal RNA enables us to discriminate between patients with and without CRC.


METHODS
The study cohort included 29 patients with CRC, and 22 control patients without neoplastic disease of the colon or rectum. RNA was isolated from routinely collected stool samples using a modified method. The expression levels of carcinoembryonic antigen (CEA) and COX-2 were determined by nested reverse-transcription polymerase chain reaction (RT-PCR).


RESULTS
The sensitivity and the specificity of fecal COX-2 assay for CRC were 90% (95% confidence interval [CI], 73%-98%) and 100% (95% CI, 85%-100%), respectively, whereas those of the fecal CEA assay for CRC were 100% (95% CI, 88%-100%) and 5% (95% CI, 2%-23%), respectively. COX-2 messenger RNA (mRNA) was detected in 3 of 4 patients with Dukes' stage A, 13 of 14 patients with Dukes' stage B, and 10 of 11 patients with Dukes' stage C or D. COX-2 mRNA was detected in 5 of 7 patients with proximal cancer and in 21 of 22 patients with distal cancer. The COX-2 assay was superior to the CEA assay for detecting CRC in terms of specificity, although both assays had high sensitivity.


CONCLUSIONS
This fecal COX-2 assay had high sensitivity and high specificity for detecting CRC. These results suggest that it would be a promising approach for detecting CRC, although a larger study is necessary to assess the sensitivity and the specificity.
First Department of Medicine, Hamamatsu University School of Medicine, Japan. kanaoka@hama-med.a.c.jp
Shigeru
S
Kanaoka
Ken-Ichi
K
Yoshida
Naoyuki
N
Miura
Haruhiko
H
Sugimura
Masayoshi
M
Kajimura
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis*; D051546:Cyclooxygenase 2; D005243:Feces; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D008403:Mass Screening / Q000379:methods*; D008565:Membrane Proteins; D008875:Middle Aged; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases