Identification of nicotinamide N-methyltransferase as a novel tumor marker for renal clear cell carcinoma.
OBJECTIVE
To explore the involvement of enzymes of drug metabolism in renal cell carcinoma we analyzed the gene expression profiles of tumor and nontumor tissues from the same patient by DNA macroarray. The enzyme nicotinamide N-methyltransferase was selected for further evaluation.


METHODS
Nicotinamide N-methyltransferase mRNA expression was investigated in paired tissue samples from cancerous and noncancerous parts of the kidneys of 30 patients with clear cell renal cell carcinoma who underwent tumor nephrectomy. Measurements were performed by semiquantitative reverse transcriptase-polymerase chain reaction and quantitative real-time polymerase chain reaction. Paired tissue samples were also obtained from 1 patient with chromophobe renal cell carcinoma and from another with oncocytoma to compare the specificity of changes in nicotinamide N-methyltransferase expression among tumors that are related to different renal epithelial cell types. Western blot analysis and catalytic activity assay were also performed to study nicotinamide N-methyltransferase expression. Expression correlated with tumor characteristics.


RESULTS
A marked increased expression in tumor tissue was found for nicotinamide N-methyltransferase, which is an enzyme involved in the biotransformation of many drugs and xenobiotic compounds. Differential gene expression measurements in tumor vs normal tissue revealed up-regulation in all clear cell renal cell carcinomas at between 3 and 294-fold (mean 41). In contrast, in chromophobe renal cell carcinoma and oncocytoma nicotinamide N-methyltransferase expression did not increase. In addition, nicotinamide N-methyltransferase expression significantly correlated inversely with tumor size.


CONCLUSIONS
Our results indicate that a marked nicotinamide N-methyltransferase increase is a peculiar feature of clear cell renal cell carcinoma. Additional studies may establish the role of nicotinamide N-methyltransferase in tumor formation and progression.
Sartini
Davide
D
Institute of Biochemical Biotechnologies, Azienda Ospedaliero-Universitaria Umberto I-Lancisi-Salesi, Ancona, Italy.
Muzzonigro
Giovanni
G
Milanese
Giulio
G
Pierella
Francesca
F
Rossi
Valentina
V
Emanuelli
Monica
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis*; D002292:Carcinoma, Renal Cell / Q000737:chemistry / Q000175:diagnosis*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000737:chemistry / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D050903:Nicotinamide N-Methyltransferase / Q000032:analysis / Q000096:biosynthesis*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D050903:Nicotinamide N-Methyltransferase