Identification of nicotinamide N-methyltransferase as a novel serum tumor marker for colorectal cancer.
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.
Roessler
Markus
M
Centralized Diagnostics, Roche Diagnostics GmbH, Penzberg, Germany.
Rollinger
Wolfgang
W
Palme
Stefan
S
Hagmann
Marie-Luise
ML
Berndt
Peter
P
Engel
Alfred M
AM
Schneidinger
Bernd
B
Pfeffer
Michael
M
Andres
Herbert
H
Karl
Johann
J
Bodenmüller
Heinz
H
Rüschoff
Josef
J
Henkel
Thomas
T
Rohr
Gerhard
G
Rossol
Siegbert
S
Rösch
Wolfgang
W
Langen
Hanno
H
Zolg
Werner
W
Tacke
Michael
M
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
D014408:Biomarkers, Tumor; D001798:Blood Proteins; D020543:Proteome; D008780:Methyltransferases; C494406:NNMT protein, human; D050903:Nicotinamide N-Methyltransferase