title: Identification of an epigenetic biomarker panel with high sensitivity and specificity for colorectal cancer and adenomas.
abstract: BACKGROUND
  The presence of cancer-specific DNA methylation patterns in epithelial colorectal cells in human feces provides the prospect of a simple, non-invasive screening test for colorectal cancer and its precursor, the adenoma. This study investigates a panel of epigenetic markers for the detection of colorectal cancer and adenomas.
  
  
  METHODS
  Candidate biomarkers were subjected to quantitative methylation analysis in test sets of tissue samples from colorectal cancers, adenomas, and normal colonic mucosa. All findings were verified in independent clinical validation series. A total of 523 human samples were included in the study. Receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of the biomarker panel.
  
  
  RESULTS
  Promoter hypermethylation of the genes CNRIP1, FBN1, INA, MAL, SNCA, and SPG20 was frequent in both colorectal cancers (65-94%) and adenomas (35-91%), whereas normal mucosa samples were rarely (0-5%) methylated. The combined sensitivity of at least two positives among the six markers was 94% for colorectal cancers and 93% for adenoma samples, with a specificity of 98%. The resulting areas under the ROC curve were 0.984 for cancers and 0.968 for adenomas versus normal mucosa.
  
  
  CONCLUSIONS
  The novel epigenetic marker panel shows very high sensitivity and specificity for both colorectal cancers and adenomas. Our findings suggest this biomarker panel to be highly suitable for early tumor detection.
authors.affiliation: Department of Cancer Prevention, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway.
authors.forename: Guro E
authors.initials: GE
authors.lastname: Lind
authors.forename: Stine A
authors.initials: SA
authors.lastname: Danielsen
authors.forename: Terje
authors.initials: T
authors.lastname: Ahlquist
authors.forename: Marianne A
authors.initials: MA
authors.lastname: Merok
authors.forename: Kim
authors.initials: K
authors.lastname: Andresen
authors.forename: Rolf I
authors.initials: RI
authors.lastname: Skotheim
authors.forename: Merete
authors.initials: M
authors.lastname: Hektoen
authors.forename: Torleiv O
authors.initials: TO
authors.lastname: Rognum
authors.forename: Gunn I
authors.initials: GI
authors.lastname: Meling
authors.forename: Geir
authors.initials: G
authors.lastname: Hoff
authors.forename: Michael
authors.initials: M
authors.lastname: Bretthauer
authors.forename: Espen
authors.initials: E
authors.lastname: Thiis-Evensen
authors.forename: Arild
authors.initials: A
authors.lastname: Nesbakken
authors.forename: Ragnhild A
authors.initials: RA
authors.lastname: Lothe
mesh_terms: D000236:Adenoma / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics / Q000302:isolation & purification*; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007413:Intestinal Mucosa / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor