Research

Expression of nicotinamide N-methyltransferase in hepatocellular carcinoma is associated with poor prognosis

Jongmin Kim¹ , Seok Joo Hong¹ , Eun Kyung Lim¹ , Yun-Suk Yu¹ , Seung Whan Kim² , Ji Hyeon Roh³ , In-Gu Do³ , Jae-Won Joh⁴ and Dae Shick Kim³

¹  Cbs Bioscience Inc., 59-5 Jang-Dong, Yuseong-gu, Daejeon, 305-343, Korea

²  Department of Emergency Medicine, Chungnam National University Hospital, Daejeon, 301-721, Korea

³  Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 135-710, Korea

⁴  Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 135-710, Korea

author email corresponding author email

Journal of Experimental & Clinical Cancer Research 2009, 28:20doi:10.1186/1756-9966-28-20

Published:	16 February 2009

Abstract

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.

Conclusion

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.