15-Hydroxyprostaglandin Dehydrogenase in Colorectal Mucosa as a Potential Biomarker for Predicting Colorectal Neoplasms

15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is downregulated during the early stages of colorectal carcinogenesis. The aim of the present study was to investigate the potential role of 15-PGDH in normal-appearing colorectal mucosa as a biomarker for predicting colorectal neoplasms. We obtained paired tumor and normal tissues from the surgical specimens of 32 sporadic colorectal cancer patients. mRNA expression of 15-PGDH was measured using a quantitative real-time PCR assay. We evaluated the association between 15-PGDH mRNA expression in normal-appearing mucosa, the presence of synchronous adenoma, and the cumulative incidence of metachronous adenoma. The relative 15-PGDH expression of normal-appearing mucosa in patients with synchronous adenoma was significantly lower than in patients without synchronous adenoma (0.71 vs 1.00, P = 0.044). The patients in the lowest tertile of 15-PGDH expression in normal-appearing mucosa were most likely to have synchronous adenoma (OR: 10.5, P = 0.024). Patients with low 15-PGDH expression in normal-appearing mucosa also demonstrated more advanced stage colorectal cancer (P = 0.045). However, there was no significant difference in the cumulative incidence of metachronous adenoma according to 15-PGDH mRNA expression in normal-appearing mucosa (P = 0.333). Hence, 15-PGDH in normal-appearing colorectal mucosa can be a useful biomarker of field effect for the prediction of sporadic synchronous neoplasms.

[1]  Heather R. Roberts,et al.  β-catenin represses expression of the tumour suppressor 15-prostaglandin dehydrogenase in the normal intestinal epithelium and colorectal tumour cells , 2011, Gut.

[2]  Young Sun Kim,et al.  Five-year risk for advanced colorectal neoplasia after initial colonoscopy according to the baseline risk stratification: a prospective study in 2452 asymptomatic Koreans , 2011, Gut.

[3]  H. Tapp,et al.  Patterns of DNA methylation in individual colonic crypts reveal aging and cancer-related field defects in the morphologically normal mucosa. , 2010, Carcinogenesis.

[4]  Y. Hu,et al.  DNA methylation within the normal colorectal mucosa is associated with pathway-specific predisposition to cancer , 2010, Oncogene.

[5]  M. Bertagnolli,et al.  Molecular origins of cancer: Molecular basis of colorectal cancer. , 2009, The New England journal of medicine.

[6]  Kyu-Won Jung,et al.  Cancer Statistics in Korea: Incidence, Mortality and Survival in 2006-2007 , 2009, Journal of Korean medical science.

[7]  Hai-rim Shin,et al.  Cancer Statistics in Korea: Incidence, Mortality and Survival in 2005 , 2009, Journal of Korean medical science.

[8]  Christopher F. Martin,et al.  Apoptosis in Normal Rectal Mucosa, Baseline Adenoma Characteristics, and Risk of Future Adenomas , 2008, Cancer Epidemiology Biomarkers & Prevention.

[9]  S. Markowitz.  Aspirin and colon cancer--targeting prevention? , 2007, The New England journal of medicine.

[10]  Raymond N DuBois,et al.  NSAIDs and cancer prevention: targets downstream of COX-2. , 2007, Annual review of medicine.

[11]  T. P. Pretlow,et al.  15-Hydroxyprostaglandin dehydrogenase is an in vivo suppressor of colon tumorigenesis , 2006, Proceedings of the National Academy of Sciences.

[12]  Gary L Rosner,et al.  Tumour vasculature: On the verge of collapse , 2005, Nature Reviews Cancer.

[13]  J. Lutterbaugh,et al.  15-Hydroxyprostaglandin dehydrogenase, a COX-2 oncogene antagonist, is a TGF-beta-induced suppressor of human gastrointestinal cancers. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[14]  C. R. Leemans,et al.  A genetic explanation of Slaughter's concept of field cancerization: evidence and clinical implications. , 2003, Cancer research.

[15]  Christopher F. Martin,et al.  Nonsteroidal anti-inflammatory drugs, apoptosis, and colorectal adenomas. , 2002, Gastroenterology.

[16]  H. Tai,et al.  Prostaglandin catabolizing enzymes. , 2002, Prostaglandins & other lipid mediators.

[17]  Rajnish A. Gupta,et al.  Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2 , 2001, Nature Reviews Cancer.

[18]  D. Henson,et al.  Biomarkers for early detection of colon cancer. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[19]  D. Alberts,et al.  Adenoma characteristics as risk factors for recurrence of advanced adenomas. , 2001, Gastroenterology.

[20]  J. Faivre,et al.  [Primary prevention of colorectal cancer]. , 1995, Bulletin du cancer.

[21]  P. gordon,et al.  Immunohistochemical expression of mutant p53 oncogene in transitional mucosa adjacent to human colon cancer. , 1993, Clinical and investigative medicine. Medecine clinique et experimentale.

[22]  S N Thibodeau,et al.  Microsatellite instability in cancer of the proximal colon. , 1993, Science.

[23]  D. Slaughter,et al.  “Field cancerization” in oral stratified squamous epithelium. Clinical implications of multicentric origin , 1953, Cancer.

[24]  A. Jemal,et al.  Cancer statistics, 2012 , 2012, CA: a cancer journal for clinicians.

[25]  A. Harłozińska,et al.  Field effect of human colon carcinoma on normal mucosa: relevance of carcinoembryonic antigen expression. , 1996, Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine.

[26]  N. Dubrawsky.  Cancer statistics , 1989, CA: a cancer journal for clinicians.