title: Identification of nicotinamide N-methyltransferase as a novel serum tumor marker for colorectal cancer.
abstract: OBJECTIVE
  The goal of this study was to identify and validate novel serum markers of human colorectal cancer as potential candidates for noninvasive detection of early colorectal neoplasm.
  
  
  METHODS
  Employing two-dimensional gel electrophoresis and mass spectrometry, we analyzed 16 matched colorectal cancer and adjacent normal tissue samples. Proteins found to be elevated in cancer tissue were further validated by generating antibodies which were used for immunoblotting of tissue samples and for the development of highly sensitive immunoassays for assessment of serum samples.
  
  
  RESULTS
  In total, 735 different proteins were identified in colon tissue. Strong elevation in colorectal cancer for five proteins was confirmed by immunoblot analysis: transforming growth factor-beta induced protein ig-h3 (betaIG-H3), nicotinamide N-methyltransferase (NNMT), nucleoside diphosphate kinase A (nm23-H1), purine nucleoside phosphorylase (PNPH), and mannose-6-phosphate receptor binding protein 1 (M6P1). Elevated levels of NNMT, which is not predicted to be secreted but is known as a cytoplasmic protein, were found in serum from patients with colorectal cancer. Employing a receiver-operating characteristic curve based on the measurement of 109 patients with colorectal cancer and 317 healthy controls, we obtained an area under the curve of 0.84 for NNMT, which was superior to the established tumor marker carcinoembryogenic antigen with an area under the curve of 0.78.
  
  
  CONCLUSIONS
  It is proposed that NNMT serum levels may have significance in the early detection and in the management of patients with colorectal cancer.
authors.affiliation: Centralized Diagnostics, Roche Diagnostics GmbH, Penzberg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Roessler
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rollinger
authors.forename: Stefan
authors.initials: S
authors.lastname: Palme
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Hagmann
authors.forename: Peter
authors.initials: P
authors.lastname: Berndt
authors.forename: Alfred M
authors.initials: AM
authors.lastname: Engel
authors.forename: Bernd
authors.initials: B
authors.lastname: Schneidinger
authors.forename: Michael
authors.initials: M
authors.lastname: Pfeffer
authors.forename: Herbert
authors.initials: H
authors.lastname: Andres
authors.forename: Johann
authors.initials: J
authors.lastname: Karl
authors.forename: Heinz
authors.initials: H
authors.lastname: Bodenmüller
authors.forename: Josef
authors.initials: J
authors.lastname: Rüschoff
authors.forename: Thomas
authors.initials: T
authors.lastname: Henkel
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rohr
authors.forename: Siegbert
authors.initials: S
authors.lastname: Rossol
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rösch
authors.forename: Hanno
authors.initials: H
authors.lastname: Langen
authors.forename: Werner
authors.initials: W
authors.lastname: Zolg
authors.forename: Michael
authors.initials: M
authors.lastname: Tacke
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D001798:Blood Proteins / Q000032:analysis; D015179:Colorectal Neoplasms / Q000097:blood* / Q000175:diagnosis; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008780:Methyltransferases / Q000097:blood*; D008875:Middle Aged; D050903:Nicotinamide N-Methyltransferase; D020543:Proteome / Q000032:analysis; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D001798:Blood Proteins; D020543:Proteome; D008780:Methyltransferases; C494406:NNMT protein, human; D050903:Nicotinamide N-Methyltransferase