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Sensitive Detection of Colorectal Cancer in Peripheral Blood by Septin 9 DNA Methylation Assay
BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer deaths despite the fact that detection of this cancer in early stages results in over 90% survival rate. Currently less than 45% of at-risk individuals in the US are screened regularly, exposing a need for better screening tes...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2582436/ https://www.ncbi.nlm.nih.gov/pubmed/19018278 http://dx.doi.org/10.1371/journal.pone.0003759 |
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author | Grützmann, Robert Molnar, Bela Pilarsky, Christian Habermann, Jens K. Schlag, Peter M. Saeger, Hans D. Miehlke, Stephan Stolz, Thomas Model, Fabian Roblick, Uwe J. Bruch, Hans-Peter Koch, Rainer Liebenberg, Volker deVos, Theo Song, Xiaoling Day, Robert H. Sledziewski, Andrew Z. Lofton-Day, Catherine |
author_facet | Grützmann, Robert Molnar, Bela Pilarsky, Christian Habermann, Jens K. Schlag, Peter M. Saeger, Hans D. Miehlke, Stephan Stolz, Thomas Model, Fabian Roblick, Uwe J. Bruch, Hans-Peter Koch, Rainer Liebenberg, Volker deVos, Theo Song, Xiaoling Day, Robert H. Sledziewski, Andrew Z. Lofton-Day, Catherine |
author_sort | Grützmann, Robert |
collection | PubMed |
description | BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer deaths despite the fact that detection of this cancer in early stages results in over 90% survival rate. Currently less than 45% of at-risk individuals in the US are screened regularly, exposing a need for better screening tests. We performed two case-control studies to validate a blood-based test that identifies methylated DNA in plasma from all stages of CRC. METHODOLOGY/PRINCIPAL FINDINGS: Using a PCR assay for analysis of Septin 9 (SEPT9) hypermethylation in DNA extracted from plasma, clinical performance was optimized on 354 samples (252 CRC, 102 controls) and validated in a blinded, independent study of 309 samples (126 CRC, 183 controls). 168 polyps and 411 additional disease controls were also evaluated. Based on the training study SEPT9-based classification detected 120/252 CRCs (48%) and 7/102 controls (7%). In the test study 73/126 CRCs (58%) and 18/183 control samples (10%) were positive for SEPT9 validating the training set results. Inclusion of an additional measurement replicate increased the sensitivity of the assay in the testing set to 72% (90/125 CRCs detected) while maintaining 90% specificity (19/183 for controls). Positive rates for plasmas from the other cancers (11/96) and non-cancerous conditions (41/315) were low. The rate of polyp detection (>1 cm) was ∼20%. CONCLUSIONS/SIGNIFICANCE: Analysis of SEPT9 DNA methylation in plasma represents a straightforward, minimally invasive method to detect all stages of CRC with potential to satisfy unmet needs for increased compliance in the screening population. Further clinical testing is warranted. |
format | Text |
id | pubmed-2582436 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-25824362008-11-19 Sensitive Detection of Colorectal Cancer in Peripheral Blood by Septin 9 DNA Methylation Assay Grützmann, Robert Molnar, Bela Pilarsky, Christian Habermann, Jens K. Schlag, Peter M. Saeger, Hans D. Miehlke, Stephan Stolz, Thomas Model, Fabian Roblick, Uwe J. Bruch, Hans-Peter Koch, Rainer Liebenberg, Volker deVos, Theo Song, Xiaoling Day, Robert H. Sledziewski, Andrew Z. Lofton-Day, Catherine PLoS One Research Article BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer deaths despite the fact that detection of this cancer in early stages results in over 90% survival rate. Currently less than 45% of at-risk individuals in the US are screened regularly, exposing a need for better screening tests. We performed two case-control studies to validate a blood-based test that identifies methylated DNA in plasma from all stages of CRC. METHODOLOGY/PRINCIPAL FINDINGS: Using a PCR assay for analysis of Septin 9 (SEPT9) hypermethylation in DNA extracted from plasma, clinical performance was optimized on 354 samples (252 CRC, 102 controls) and validated in a blinded, independent study of 309 samples (126 CRC, 183 controls). 168 polyps and 411 additional disease controls were also evaluated. Based on the training study SEPT9-based classification detected 120/252 CRCs (48%) and 7/102 controls (7%). In the test study 73/126 CRCs (58%) and 18/183 control samples (10%) were positive for SEPT9 validating the training set results. Inclusion of an additional measurement replicate increased the sensitivity of the assay in the testing set to 72% (90/125 CRCs detected) while maintaining 90% specificity (19/183 for controls). Positive rates for plasmas from the other cancers (11/96) and non-cancerous conditions (41/315) were low. The rate of polyp detection (>1 cm) was ∼20%. CONCLUSIONS/SIGNIFICANCE: Analysis of SEPT9 DNA methylation in plasma represents a straightforward, minimally invasive method to detect all stages of CRC with potential to satisfy unmet needs for increased compliance in the screening population. Further clinical testing is warranted. Public Library of Science 2008-11-19 /pmc/articles/PMC2582436/ /pubmed/19018278 http://dx.doi.org/10.1371/journal.pone.0003759 Text en Grützmann et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Grützmann, Robert Molnar, Bela Pilarsky, Christian Habermann, Jens K. Schlag, Peter M. Saeger, Hans D. Miehlke, Stephan Stolz, Thomas Model, Fabian Roblick, Uwe J. Bruch, Hans-Peter Koch, Rainer Liebenberg, Volker deVos, Theo Song, Xiaoling Day, Robert H. Sledziewski, Andrew Z. Lofton-Day, Catherine Sensitive Detection of Colorectal Cancer in Peripheral Blood by Septin 9 DNA Methylation Assay |
title | Sensitive Detection of Colorectal Cancer in Peripheral Blood by Septin 9 DNA Methylation Assay |
title_full | Sensitive Detection of Colorectal Cancer in Peripheral Blood by Septin 9 DNA Methylation Assay |
title_fullStr | Sensitive Detection of Colorectal Cancer in Peripheral Blood by Septin 9 DNA Methylation Assay |
title_full_unstemmed | Sensitive Detection of Colorectal Cancer in Peripheral Blood by Septin 9 DNA Methylation Assay |
title_short | Sensitive Detection of Colorectal Cancer in Peripheral Blood by Septin 9 DNA Methylation Assay |
title_sort | sensitive detection of colorectal cancer in peripheral blood by septin 9 dna methylation assay |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2582436/ https://www.ncbi.nlm.nih.gov/pubmed/19018278 http://dx.doi.org/10.1371/journal.pone.0003759 |
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