Expression of nicotinamide N-methyltransferase in hepatocellular carcinoma is associated with poor prognosis.
BACKGROUND
Hepatocellular carcinoma (HCC) is the most common tumor in the adult liver, with high relapse and mortality rates despite diverse treatment modalities. In this study, nicotinamide N-methyltransferase (NNMT), a key enzyme in drug metabolism, was investigated as a potential prognostic factor.


METHODS
Frozen tumors and non-cancerous surrounding tissues from 120 patients with primary HCC were studied. Expressions of NNMT and internal control genes were measured by real-time reverse-transcription PCR (RT-PCR). The relationship of NNMT mRNA level with clinicopathologic parameters and clinical outcome was evaluated.


RESULTS
NNMT mRNA level is markedly reduced in HCCs compared to non-cancerous surrounding tissues (P < 0.0001), and NNMT expression in tumors was significantly correlated with tumor stage (P = 0.010). Moreover, stratification of patients based on tumor NNMT mRNA levels revealed that the patients who expressed higher NNMT mRNA levels tended to have a shorter overall survival (OS) time (P = 0.053) and a significantly shorter disease-free survival (DFS) time (P = 0.016). Both NNMT expression (P = 0.0096) and tumor stage (P = 0.0017) were found to be significant prognostic factors for DFS in a multivariate analysis.


CONCLUSIONS
The results of this study indicated that NNMT gene expression is associated with tumor stage and DFS time in HCC cases. Because of the broad substrate specificity of NNMT, which could alter the efficacy and adverse effects of chemotherapy, NNMT merits further investigation regarding its role as a prognostic factor with a larger cohort of HCC patients.
Kim
Jongmin
J
Cbs Bioscience Inc., Yuseong-gu, Daejeon, Korea. jkim@cbsbio.com
Hong
Seok Joo
SJ
Lim
Eun Kyung
EK
Yu
Yun-Suk
YS
Kim
Seung Whan
SW
Roh
Ji Hyeon
JH
Do
In-Gu
IG
Joh
Jae-Won
JW
Kim
Dae Shick
DS
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D050903:Nicotinamide N-Methyltransferase / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D055815:Young Adult
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C494406:NNMT protein, human; D050903:Nicotinamide N-Methyltransferase