Analysis of promoter methylation in stool: A novel method for the detection of colorectal cancer

Lenhard, Konstanze; Bommer, Guido T.; Asutay, S; Schauer, Rolf; Brabletz, Thomas; Göke, Burkhard; Lamerz, R.; Kolligs, Frank T.

doi:10.1016/s1542-3565(04)00624-x

Cited by 112 publications

(77 citation statements)

References 44 publications

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“…Detection of CpG island methylation in human DNA isolated from stool (Belshaw et al, 2004;Leung et al, 2004;Chen et al, 2005;Zitt et al, 2007) or serum (Zou et al, 2002;Leung et al, 2005;Nakayama et al, 2007;Lofton-Day et al, 2008) has been proposed as a new strategy for the early diagnosis of colorectal neoplasia. Other studies with comparable series have reported high sensitivities for different methylation markers used alone (Chen et al, 2005;Lenhard et al, 2005;Huang et al, 2007a;Wang and Tang, 2008) or in combination (Leung et al, 2004;Petko et al, 2005;Huang et al, 2007b;Lofton-Day et al, 2008), although a wider application is usually hinder by a limited specificity.…”

Section: Discussionmentioning

confidence: 91%

Long-range epigenetic silencing at 2q14.2 affects most human colorectal cancers and may have application as a non-invasive biomarker of disease

et al. 2009

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Large chromosomal regions can be suppressed in cancer cells as denoted by hypermethylation of neighbouring CpG islands and downregulation of most genes within the region. We have analysed the extent and prevalence of long-range epigenetic silencing at 2q14.2 (the first and best characterised example of coordinated epigenetic remodelling) and investigated its possible applicability as a non-invasive diagnostic marker of human colorectal cancer using different approaches and biological samples. Hypermethylation of at least one of the CpG islands analysed (EN1, SCTR, INHBB) occurred in most carcinomas (90%), with EN1 methylated in 73 and 40% of carcinomas and adenomas, respectively. Gene suppression was a common phenomenon in all the tumours analysed and affected both methylated and unmethylated genes. Detection of methylated EN1 using bisulfite treatment and melting curve (MC) analysis from stool DNA in patients and controls resulted in a predictive capacity of, 44% sensitivity in positive patients (27% of overall sensitivity) and 97% specificity. We conclude that epigenetic suppression along 2q14.2 is common to most colorectal cancers and the presence of a methylated EN1 CpG island in stool DNA might be used as biomarker of neoplastic disease.

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Section: Discussionmentioning

confidence: 91%

Long-range epigenetic silencing at 2q14.2 affects most human colorectal cancers and may have application as a non-invasive biomarker of disease

et al. 2009

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“…The studies that evaluated the standard guaiac-based FOBT that did not correct for verification bias are listed in Table 1. [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50] In the last study, the data was presented in two separate publications. These 19 studies included 713 subjects with colorectal cancer and 4181 controls.…”

Section: Included Studiesmentioning

confidence: 99%

“…Most studies included subjects who submitted 3 stool specimens [31][32][33][34]36,37,39,41,44,[46][47][48][49][50] while some studies included subjects who only submitted one specimen 35,42,43 or the number was not specified. 38,40,45 Almost all of the studies reported that the specimens were collected at home while one study did not specify the location. 38 The studies listed in Table 1 recruited subjects by two methods: inclusion of patients undergoing colonoscopy for a variety of indications (e.g., FOBT positivity, GI symptoms, colon cancer screening, polyp surveillance) [31][32][33][34][35][36][37][38][39]41,[44][45][46][47] or selection of a group of known colorectal cancer patients and controls undergoing colonoscopy.…”

Section: Included Studiesmentioning

confidence: 99%

“…38 The studies listed in Table 1 recruited subjects by two methods: inclusion of patients undergoing colonoscopy for a variety of indications (e.g., FOBT positivity, GI symptoms, colon cancer screening, polyp surveillance) [31][32][33][34][35][36][37][38][39]41,[44][45][46][47] or selection of a group of known colorectal cancer patients and controls undergoing colonoscopy. 40,42,43,[48][49][50] Both of these methods contain potential verification bias as not all of the FOBT negative patients in the population underwent a confirmatory test. The studies that attempted to reduce verification bias are listed in Table 2.…”

Section: Included Studiesmentioning

confidence: 99%

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Effect of Verification Bias on the Sensitivity of Fecal Occult Blood Testing: a Meta-Analysis

Rosman

Korsten

2010

J GEN INTERN MED

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OBJECTIVES: There is controversy regarding the sensitivity of fecal occult blood tests (FOBT) for detecting colorectal cancer. Many of the published studies failed to correct for verification bias which may have increased the sensitivity. METHODS: A meta-analysis of published studies evaluating the sensitivity and specificity of chemical-based FOBT for colorectal cancer was performed. Studies were included if both cancer and control subjects underwent confirmatory testing. We also included studies that attempted to correct for verification bias by either performing colonoscopy on all subjects regardless of the FOBT result or by using longitudinal follow-up. We then compared the sensitivity, specificity, and other diagnostic characteristics of the studies that attempted to correct for verification (n=10) vs. those that did not correct for this bias (n=19). RESULTS: The pooled sensitivity of guaiac-based FOBT for colorectal cancer of studies without verification bias was significantly lower than those studies with this bias There was no significant difference in the area under the summary receiver operating characteristic curves. More sensitive chemical-based FOBT methods (e.g., Hemoccult® SENSA®) had a higher sensitivity but a lower specificity than standard guaiac methods. CONCLUSIONS: The sensitivity of guaiac-based FOBT for colorectal cancer has been overestimated as a result of verification bias. This test may not be sensitive enough to serve as an effective screening option for colorectal cancer.KEY WORDS: fecal occult blood; guaiac; colorectal cancer; summary receiver operating characteristic curve; meta-analysis.

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“…Moreover, guaiac FOBT tests require patients to change their diet before testing, 18 FOBT: Is currently widely used because it is convenient and not costly, but it has low sensitivity and requires multiple sampling, which reduces compliance [21,23,25,27,29,32] ■ Methylated Gene: Only good for detection of advanced cancer, but not adenoma, based on vimentin gene, DY loci 5p21 and C91199, thus it is not suitable for population screening [39]. ♦ Promoter Methylation: Based on only one gene and is basically a specialized procedure for research purpose, thus not suited for population screening [40].…”

Section: Current Methods For Colon Cancer Screeningmentioning

confidence: 99%

MicroRNAs as molecular markers for colon cancer Diagnostic screening in stool & blood

Ahmed¹,

Ahmed²

2017

Med Res Innov

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Screening for colon cancer (CC) allows for diagnosis of the early stage for malignancy and potentially reduces disease mortality as the cancer could be cured at disease earliest stages. Early detection could be desirable if accurate, practical and cost effective diagnostic measures for this cancer are available. Mortality and morbidity from colon cancer represent a major health problem involving a malignant disease that is theoretically preventable through screening. Current screening methods (e.g., the immunological fecal occult blood test, FOBTi, obtained from patients' medical records) either lacks sensitivity and requires dietary restriction, which impedes compliance and use; are costly (e.g., colonoscopy), which decreases compliance; or could lead to mortality. In comparison to the FOBT test, a noninvasive sensitive screen for which there is no requirement for dietary restriction would be a more convenient test. Colorectal cancer (CRC) is the only cancer for which screening by colonoscopy is recommended. Although colonoscopy is a reliable screening tool, its invasive nature, accompanying abdominal pain, potential complications and high cost have hampered the application of this screening method worldwide.A novel screening approach using the stable miRNA molecules, which are relatively nondegradable when extracted from noninvasive stool and semi-invasive blood samples by currently available commercial kits and manipulated thereafter, would be preferable to a transcriptomic messenger (m)RNA-, a mutation DNA-, an epigenetic-or a proteomic-based test. The approach utilizes reverse transcriptase (RT), followed by a modified quantitative real-time polymerase chain reaction (qPCR). Although exosomal RNA would not be measured, using a restricted extraction of total RNA from stool or blood, then a parallel test could also be carried out on RNA obtained from stool or plasma samples, and appropriate corrections for exsosomal loss can be made to obtain accurate and quantitative results. Eventually, a chip would be developed to facilitate diagnosis, as has been carried out for the quantification of genetically modified organisms (GMOs) in foods. The gold standard to which the molecular miRNA test is compared is colonoscopy. If performance criteria are met, as detailed herein, then a miRNA test in human stool or blood samples based on high throughput automated technologies and quantitative expression measurements --commonly used in the diagnostic clinical laboratory--would eventually be advanced to the clinical setting, which will make a vivid impact on the prevention of colon cancer.Correspondence to: Farid E. Ahmed, GEM

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Analysis of promoter methylation in stool: A novel method for the detection of colorectal cancer

Cited by 112 publications

References 44 publications

Long-range epigenetic silencing at 2q14.2 affects most human colorectal cancers and may have application as a non-invasive biomarker of disease

Long-range epigenetic silencing at 2q14.2 affects most human colorectal cancers and may have application as a non-invasive biomarker of disease

Effect of Verification Bias on the Sensitivity of Fecal Occult Blood Testing: a Meta-Analysis

MicroRNAs as molecular markers for colon cancer Diagnostic screening in stool & blood

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