title: Sensitive detection of colorectal cancer in peripheral blood by septin 9 DNA methylation assay.
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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Visceral-, Thoracic- and Vascular Surgery, University Hospital Carl Gustav Carus Dresden, Dresden, Germany. Robert.Gruetzmann@uniklinikum-dresden.de
authors.forename: Robert
authors.initials: R
authors.lastname: Grützmann
authors.forename: Bela
authors.initials: B
authors.lastname: Molnar
authors.forename: Christian
authors.initials: C
authors.lastname: Pilarsky
authors.forename: Jens K
authors.initials: JK
authors.lastname: Habermann
authors.forename: Peter M
authors.initials: PM
authors.lastname: Schlag
authors.forename: Hans D
authors.initials: HD
authors.lastname: Saeger
authors.forename: Stephan
authors.initials: S
authors.lastname: Miehlke
authors.forename: Thomas
authors.initials: T
authors.lastname: Stolz
authors.forename: Fabian
authors.initials: F
authors.lastname: Model
authors.forename: Uwe J
authors.initials: UJ
authors.lastname: Roblick
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Bruch
authors.forename: Rainer
authors.initials: R
authors.lastname: Koch
authors.forename: Volker
authors.initials: V
authors.lastname: Liebenberg
authors.forename: Theo
authors.initials: T
authors.lastname: Devos
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Song
authors.forename: Robert H
authors.initials: RH
authors.lastname: Day
authors.forename: Andrew Z
authors.initials: AZ
authors.lastname: Sledziewski
authors.forename: Catherine
authors.initials: C
authors.lastname: Lofton-Day
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D020558:GTP Phosphohydrolases / Q000097:blood / Q000235:genetics*; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D058112:Septins; D016896:Treatment Outcome
chemical_list: D020558:GTP Phosphohydrolases; C474315:SEPTIN9 protein, human; D058112:Septins