Sensitive Detection of Colorectal Cancer in Peripheral Blood by Septin 9 DNA Methylation Assay Export

@article{citeulike:3644304, abstract = {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.}, author = {Gr\"{u}tzmann, Robert and Molnar, Bela and Pilarsky, Christian and Habermann, Jens K. and Schlag, Peter M. and Saeger, Hans D. and Miehlke, Stephan and Stolz, Thomas and Model, Fabian and Roblick, Uwe J. and Bruch, Hans-Peter and Koch, Rainer and Liebenberg, Volker and Devos, Theo and Song, Xiaoling and Day, Robert H. and Sledziewski, Andrew Z. and Lofton-Day, Catherine}, citeulike-article-id = {3644304}, citeulike-linkout-0 = {http://dx.doi.org/10.1371/journal.pone.0003759}, day = {19}, doi = {10.1371/journal.pone.0003759}, journal = {PLoS ONE}, keywords = {biomarker, blood, cancer, colon, colorectal, serum}, month = {November}, number = {11}, pages = {e3759+}, posted-at = {2008-11-21 11:25:48}, priority = {0}, publisher = {Public Library of Science}, title = {Sensitive Detection of Colorectal Cancer in Peripheral Blood by Septin 9 DNA Methylation Assay}, url = {http://dx.doi.org/10.1371/journal.pone.0003759}, volume = {3}, year = {2008} }

TY - JOUR ID - citeulike:3644304 L3 - citeulike-article-id:3644304 N2 - 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. IS - 11 JF - PLoS ONE TI - Sensitive Detection of Colorectal Cancer in Peripheral Blood by Septin 9 DNA Methylation Assay PB - Public Library of Science VL - 3 SP - e3759 KW - biomarker KW - blood KW - cancer KW - colon KW - colorectal KW - serum AU - Grützmann, Robert AU - Molnar, Bela AU - Pilarsky, Christian AU - Habermann, Jens AU - Schlag, Peter AU - Saeger, Hans AU - Miehlke, Stephan AU - Stolz, Thomas AU - Model, Fabian AU - Roblick, Uwe AU - Bruch, Hans-Peter AU - Koch, Rainer AU - Liebenberg, Volker AU - Devos, Theo AU - Song, Xiaoling AU - Day, Robert AU - Sledziewski, Andrew AU - Lofton-Day, Catherine PY - 2008/11/19/ UR - http://dx.doi.org/10.1371/journal.pone.0003759 ER -