title: Methylation of NEUROG1 in serum is a sensitive marker for the detection of early colorectal cancer.
abstract: OBJECTIVE
  Colorectal cancer is the third most common cancer and a major cause of cancer-related deaths. Early detection of colonic lesions can reduce the incidence and mortality of colorectal cancer. Colonoscopy is the screening test for colorectal cancer with the highest efficacy, but its acceptance in the general public is rather low. To identify suitable tumor-derived markers that could detect colorectal cancer in blood samples, we analyzed the methylation status of a panel of genes in sera of affected patients.
  
  
  METHODS
  Using methylation-specific quantitative PCR, we analyzed the methylation of ten marker genes in sera of healthy individuals and patients with colorectal cancer.
  
  
  RESULTS
  Only HLTF, HPP1/TPEF, and NEUROG1 DNA methylation was detectable in at least 50% of patients with colorectal cancers. Whereas HLTF and HPP1/TPEF preferentially detected advanced and metastasized colorectal cancers, NEUROG1 methylation was detectable in UICC stages I-IV at a similar rate. Compared with other methylation markers, such as ALX4, SEPT9, and vimentin, NEUROG1 shows a higher sensitivity for colorectal cancer at UICC stages I and II. At a specificity of 91%, NEUROG1 reached a sensitivity of 61% (confidence interval, 50.4-70.6%) for the detection of colorectal cancers. Furthermore, detection of NEUROG1 methylation was independent of age and gender.
  
  
  CONCLUSIONS
  Methylation of the NEUROG1 gene is frequently found in sera of patients with colorectal cancers independent of tumor stage. The quantitative detection of NEUROG1 DNA methylation in serum is a suitable approach for the non-invasive screening for asymptomatic colorectal cancer.
authors.affiliation: Department of Medicine II, University of Munich, Munich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Herbst
authors.forename: Konstanze
authors.initials: K
authors.lastname: Rahmig
authors.forename: Petra
authors.initials: P
authors.lastname: Stieber
authors.forename: Alexander
authors.initials: A
authors.lastname: Philipp
authors.forename: Andreas
authors.initials: A
authors.lastname: Jung
authors.forename: Andrea
authors.initials: A
authors.lastname: Ofner
authors.forename: Alexander
authors.initials: A
authors.lastname: Crispin
authors.forename: Jens
authors.initials: J
authors.lastname: Neumann
authors.forename: Rolf
authors.initials: R
authors.lastname: Lamerz
authors.forename: Frank T
authors.initials: FT
authors.lastname: Kolligs
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051792:Basic Helix-Loop-Helix Proteins / Q000097:blood / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000032:analysis*; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000097:blood / Q000235:genetics*; D010865:Pilot Projects; D012372:ROC Curve; D012016:Reference Values; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D009419:Nerve Tissue Proteins; C105389:NEUROG1 protein, human