PLoS ONE (Jan 2008)

Sensitive detection of colorectal cancer in peripheral blood by septin 9 DNA methylation assay.

  • Robert Grützmann,
  • Bela Molnar,
  • Christian Pilarsky,
  • Jens K Habermann,
  • Peter M Schlag,
  • Hans D Saeger,
  • Stephan Miehlke,
  • Thomas Stolz,
  • Fabian Model,
  • Uwe J Roblick,
  • Hans-Peter Bruch,
  • Rainer Koch,
  • Volker Liebenberg,
  • Theo Devos,
  • Xiaoling Song,
  • Robert H Day,
  • Andrew Z Sledziewski,
  • Catherine Lofton-Day

DOI
https://doi.org/10.1371/journal.pone.0003759
Journal volume & issue
Vol. 3, no. 11
p. e3759

Abstract

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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 approximately 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.