Fecal Cyclooxygenase 2 Plus Matrix Metalloproteinase 7 mRNA Assays as a Marker for Colorectal Cancer Screening

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 18; no. 6; pp. 1888 - 1893
• Main Authors: Takai, Tetsunari, Kanaoka, Shigeru, Yoshida, Ken-ichi, Hamaya, Yasushi, Ikuma, Mutsuhiro, Miura, Naoyuki, Sugimura, Haruhiko, Kajimura, Masayoshi, Hishida, Akira
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.06.2009
• Subjects: Aged; Aged, 80 and over; Biological and medical sciences; Biomarkers, Tumor - analysis; Carcinoembryonic Antigen - analysis; Carcinoembryonic Antigen - genetics; colorectal cancer; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - enzymology; Colorectal Neoplasms - genetics; COX-2; Cyclooxygenase 2 - analysis; Cyclooxygenase 2 - genetics; Early Detection of Cancer; feces; Feces - chemistry; Feces - enzymology; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Immunohistochemistry; Male; Mass Screening - methods; Matrix Metalloproteinase 7 - analysis; Matrix Metalloproteinase 7 - genetics; Medical sciences; Middle Aged; MMP-7; Neoplasm Staging; Occult Blood; Reverse Transcriptase Polymerase Chain Reaction; RNA; RNA, Messenger - analysis; Sensitivity and Specificity; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Rectal disease; Enzyme; Cyclooxygenase 2; Colorectal cancer; Biological marker; Metalloendopeptidases; Malignant tumor; Medical screening; Gelatinase A; Colonic disease; Assay; Peptidases; Cancerology; Messenger RNA; Hydrolases; Digestive diseases; Intestinal disease; Oxidoreductases; Feces; Cancer
• ISSN: 1055-9965; 1538-7755; 1538-7755
• DOI: 10.1158/1055-9965.EPI-08-0937

We previously reported that fecal cyclooxygenase 2 (COX-2) mRNA assay, detecting COX-2 mRNA in feces, is useful for identifying subjects with colorectal cancer (CRC). To further improve the sensitivity, we evaluated the usefulness of the combination of COX-2 mRNA and matrix metalloproteinase 7 (MMP-7) mRNA assays as a marker of CRC. The study cohort included 62 patients with CRC and 29 control patients without colorectal neoplasia. RNA was isolated from routinely collected fecal samples. The expression levels of COX-2 and MMP-7 mRNAs were determined by nested reverse transcription-PCR. PCR conditions were optimized where the specificity of fecal COX-2 and MMP-7 mRNA assay result in 100%. The sensitivity of each fecal assay was 87% [95% confidence interval (95% CI), 76-94%] and 65% (95% CI, 51-76%) for CRC, respectively. The sensitivity of fecal RNA test (either marker being positive) was high for CRC (90%; 95% CI, 80-96%). The sensitivity of the fecal RNA test was also high (93%; 95% CI, 80-98%) in patients with stage I or II who are often cured by surgical resection. The fecal RNA test using COX-2 and MMP-7 mRNAs improved the sensitivity to detect CRC without decreasing the specificity. These results suggest that the fecal RNA test would be a promising approach for CRC screening, although larger clinical investigations are indicated. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1888–93)