Skip to main content
Top
Published in: Digestive Diseases and Sciences 9/2007

01-09-2007 | Original Paper

Hypermethylation of SFRP2 as a Potential Marker for Stool-Based Detection of Colorectal Cancer and Precancerous Lesions

Authors: Zhaohui Huang, Lihua Li, Jinfu Wang

Published in: Digestive Diseases and Sciences | Issue 9/2007

Login to get access

Abstract

DNA methylation is a key mechanism of colorectal carcinogenesis. Analysis of aberrantly methylation in stool DNA might provide a novel strategy for noninvasive detection of colorectal cancer (CRC). To explore the feasibility of this approach, we have assessed the methylation status of secreted frizzled-related protein gene 2 (SFRP2) in stool samples from patients with CRC with respect to a series of healthy individuals and patients with benign colorectal diseases, using methylation-specific polymerase chain reaction. Methylated SFRP2 occurs in 94.2%, 52.4%, 37.5%, and 16.7% of patients with CRC, adenomas, hyperplstic polyps, and ulcerative colitis, respectively. Of the 24 normal individuals, only 1 revealed methylated DNA. The pilot study revealed that aberrant methylated SFRP2 could be detected frequently in stools from patients with CRC and precancerous lesions. Methylation testing of fecal DNA may be a simple, promising, and noninvasive screening tool for colorectal neoplasia.
Literature
1.
go back to reference Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ (2006) Cancer statistics. CA Cancer J Clin 56:106–130PubMed Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ (2006) Cancer statistics. CA Cancer J Clin 56:106–130PubMed
2.
go back to reference Syngal S, Chung D, Willett C, Schoetz D, Schroy P, Stoffel E, Jagadeesh D, Morel K, Ross M (2002) Stool DNA analysis for the detection and follow-up of colorectal cancer (CRC) and advanced adenomas (AA): sensitivity in a prospective series. Am J Gastroenterol 197(Suppl):S109CrossRef Syngal S, Chung D, Willett C, Schoetz D, Schroy P, Stoffel E, Jagadeesh D, Morel K, Ross M (2002) Stool DNA analysis for the detection and follow-up of colorectal cancer (CRC) and advanced adenomas (AA): sensitivity in a prospective series. Am J Gastroenterol 197(Suppl):S109CrossRef
3.
go back to reference Ahlquist DA, Skoletsky JE, Boynton KA, Harrington JJ, Mahoney DW, Pierceall WE, Thibodeau SN, Shuber AP (2000) Colorectal cancer screening by detection of altered human DNA in stool: feasibility of a multitarget assay panel. Astroenterology 119:1219–1227CrossRef Ahlquist DA, Skoletsky JE, Boynton KA, Harrington JJ, Mahoney DW, Pierceall WE, Thibodeau SN, Shuber AP (2000) Colorectal cancer screening by detection of altered human DNA in stool: feasibility of a multitarget assay panel. Astroenterology 119:1219–1227CrossRef
4.
go back to reference Dong SM, Traverso G, Johnson C, Geng L, Favis R, Boynton K, Hibi K, Goodman SN, D’Allessio M, Paty P, Hamilton SR, Sidransky D, Barany F, Levin B, Shuber A, Kinzler KW, Vogelstein B, Jen J (2001) Detecting colorectal cancer in stool with the use of multiple genetic targets. J Natl Cancer Inst 93:858–865PubMedCrossRef Dong SM, Traverso G, Johnson C, Geng L, Favis R, Boynton K, Hibi K, Goodman SN, D’Allessio M, Paty P, Hamilton SR, Sidransky D, Barany F, Levin B, Shuber A, Kinzler KW, Vogelstein B, Jen J (2001) Detecting colorectal cancer in stool with the use of multiple genetic targets. J Natl Cancer Inst 93:858–865PubMedCrossRef
5.
go back to reference Tagore KS, Lawson MJ, Yucaitis JA, Gage R, Orr T, Shuber AP, Ross ME (2003) Sensitivity and specificity of a stool DNA: multitarget assay panel for the detection of advanced colorectal neoplasia. Clin Colorectal Cancer 3:47–53PubMedCrossRef Tagore KS, Lawson MJ, Yucaitis JA, Gage R, Orr T, Shuber AP, Ross ME (2003) Sensitivity and specificity of a stool DNA: multitarget assay panel for the detection of advanced colorectal neoplasia. Clin Colorectal Cancer 3:47–53PubMedCrossRef
6.
go back to reference Jones PA, Baylin SB (2002) The fundamental role of epigenetic events in cancer. Nat Rev Genet 3:415–428PubMedCrossRef Jones PA, Baylin SB (2002) The fundamental role of epigenetic events in cancer. Nat Rev Genet 3:415–428PubMedCrossRef
7.
go back to reference Baylin SB, Ohm JE (2006) Epigenetic gene silencing in cancer—a mechanism for early oncogenic pathway addiction? Nature 6:107–116 Baylin SB, Ohm JE (2006) Epigenetic gene silencing in cancer—a mechanism for early oncogenic pathway addiction? Nature 6:107–116
8.
9.
go back to reference Chan AO, Broaddus RR, Houlihan PS, Issa JP, Hamilton SR, Rashid A (2002) CpG island methylation in aberrant crypt foci of the colorectum. Am J Pathol 160:1823–1830PubMed Chan AO, Broaddus RR, Houlihan PS, Issa JP, Hamilton SR, Rashid A (2002) CpG island methylation in aberrant crypt foci of the colorectum. Am J Pathol 160:1823–1830PubMed
10.
go back to reference Belshaw NJ, Elliott GO, Williams EA, Bradburn DM, Mills SJ, Mathers JC, Johnson IT (2004) Use of DNA from human stools to detect aberrant CpG island methylation of genes implicated in colorectal cancer. Cancer Epidemiol Biomarkers Prev 13:1495–150PubMed Belshaw NJ, Elliott GO, Williams EA, Bradburn DM, Mills SJ, Mathers JC, Johnson IT (2004) Use of DNA from human stools to detect aberrant CpG island methylation of genes implicated in colorectal cancer. Cancer Epidemiol Biomarkers Prev 13:1495–150PubMed
11.
go back to reference Leung WK, To KF, Man EP, Chan MW, Bai AH, Hui AJ, Chan FK, Lee JF, Sung JJ (2004) Detection of epigenetic changes in fecal DNA as a molecular screening test for colorectal cancer: a feasibility study. Clin Chem 50:2179–2182PubMedCrossRef Leung WK, To KF, Man EP, Chan MW, Bai AH, Hui AJ, Chan FK, Lee JF, Sung JJ (2004) Detection of epigenetic changes in fecal DNA as a molecular screening test for colorectal cancer: a feasibility study. Clin Chem 50:2179–2182PubMedCrossRef
12.
go back to reference Müller HM, Oberwalder M, Fiegl H, Morandell M, Goebel G, Zitt M, Mühlthaler M, Öfner D, Margreiter R, Widschwendter M (2004) Methylation changes in faecal DNA: a marker for colorectal cancer screening? Lancet 363:1283–1285PubMedCrossRef Müller HM, Oberwalder M, Fiegl H, Morandell M, Goebel G, Zitt M, Mühlthaler M, Öfner D, Margreiter R, Widschwendter M (2004) Methylation changes in faecal DNA: a marker for colorectal cancer screening? Lancet 363:1283–1285PubMedCrossRef
13.
go back to reference Petko Z, Ghiassi M, Shuber A, Gorham J, Smalley W, Washington MK, Schultenover S, Gautam S, Markowitz SD, Grady WM (2005) Aberrantly methylated CDKN2A, MGMT, and MLH1 in colon polyps and in fecal DNA from patients with colorectal polyps. Clin Cancer Res 11:1203–1209PubMed Petko Z, Ghiassi M, Shuber A, Gorham J, Smalley W, Washington MK, Schultenover S, Gautam S, Markowitz SD, Grady WM (2005) Aberrantly methylated CDKN2A, MGMT, and MLH1 in colon polyps and in fecal DNA from patients with colorectal polyps. Clin Cancer Res 11:1203–1209PubMed
14.
go back to reference Lenhard K, Bommer GT, Asutay S, Schauer R, Brabletz T, Göke B, Lamerz R, Kolligs FT (2005) Analysis of promoter methylation in stool: a novel method for the detection of colorectal cancer. Clin Gastroenterol Hepatol 3:142–149PubMedCrossRef Lenhard K, Bommer GT, Asutay S, Schauer R, Brabletz T, Göke B, Lamerz R, Kolligs FT (2005) Analysis of promoter methylation in stool: a novel method for the detection of colorectal cancer. Clin Gastroenterol Hepatol 3:142–149PubMedCrossRef
15.
go back to reference Herman JG, Graff JR, Myöhänen S, Nelkin BD, Baylin SB (1996) Methylation-specific PCR, a novel PCR assay for methylation Status of CpG islands. Proc Natl Acad Sci USA 93:9821–9826PubMedCrossRef Herman JG, Graff JR, Myöhänen S, Nelkin BD, Baylin SB (1996) Methylation-specific PCR, a novel PCR assay for methylation Status of CpG islands. Proc Natl Acad Sci USA 93:9821–9826PubMedCrossRef
16.
go back to reference Suzuki H, Gabrielson E, Chen W, Anbazhagan R, van Engeland M, Weijenberg MP, Herman JG, Baylin SB (2002) A genomic screen for genes upregulated by demethylation and histone deacetylase inhibition in human colorectal cancer. Nat Genet 31:141–149PubMedCrossRef Suzuki H, Gabrielson E, Chen W, Anbazhagan R, van Engeland M, Weijenberg MP, Herman JG, Baylin SB (2002) A genomic screen for genes upregulated by demethylation and histone deacetylase inhibition in human colorectal cancer. Nat Genet 31:141–149PubMedCrossRef
17.
go back to reference Suzuki H, Watkins DN, Jair KW, Schuebel KE, Markowitz SD, Dong Chen W, Pretlow TP, Yang B, Akiyama Y, Van Engeland M, Toyota M, Tokino T, Hinoda Y, Imai K, Herman JG, Baylin SB (2004) Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer. Nat Genet 36:417–422PubMedCrossRef Suzuki H, Watkins DN, Jair KW, Schuebel KE, Markowitz SD, Dong Chen W, Pretlow TP, Yang B, Akiyama Y, Van Engeland M, Toyota M, Tokino T, Hinoda Y, Imai K, Herman JG, Baylin SB (2004) Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer. Nat Genet 36:417–422PubMedCrossRef
18.
19.
go back to reference Wynter CV, Walsh MD, Higuchi T, Leggett BA, Young J, Jass JR (2004) Methylation patterns define two types of hyperplastic polyp associated with colorectal cancer. Gut 53:573–580PubMedCrossRef Wynter CV, Walsh MD, Higuchi T, Leggett BA, Young J, Jass JR (2004) Methylation patterns define two types of hyperplastic polyp associated with colorectal cancer. Gut 53:573–580PubMedCrossRef
20.
go back to reference Pabby AJ, Suneja A, Heeren T, Farraye FA (2005) Flexible sigmoidoscopy for colorectal cancer screening in the elderly. Dig Dis Sci 50:2147–2152PubMedCrossRef Pabby AJ, Suneja A, Heeren T, Farraye FA (2005) Flexible sigmoidoscopy for colorectal cancer screening in the elderly. Dig Dis Sci 50:2147–2152PubMedCrossRef
Metadata
Title
Hypermethylation of SFRP2 as a Potential Marker for Stool-Based Detection of Colorectal Cancer and Precancerous Lesions
Authors
Zhaohui Huang
Lihua Li
Jinfu Wang
Publication date
01-09-2007
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 9/2007
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-007-9755-y

Other articles of this Issue 9/2007

Digestive Diseases and Sciences 9/2007 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine